Innate Lymphoid Cells in Tissue Homeostasis and Diseases

Abstract

Innate lymphoid cells (ILCs) are tissue-resident immune sentinels that play pivotal roles in maintaining tissue homeostasis, orchestrating immune responses, and modulating metabolic balance. They rapidly respond to environmental cues and interplay with other immune cells, thereby mediating host defense and facilitating tissue repair. However, dysregulation of ILC responses is increasingly implicated in the pathogenesis of a broad spectrum of diseases. This review provides a comprehensive overview of ILC biology, beginning with their classification, plasticity, and homeostatic functions. We then dissect the complex, dual roles of ILCs across various pathological conditions. Using sepsis as a paradigmatic example of immune dysregulation, we illustrate how ILCs orchestrate both protective immunity and pathological role in a context-dependent manner. Furthermore, we extend the discussion to cancer, chronic inflammatory diseases, and metabolic disorders, highlighting the tissue-specific functions of ILC subsets. Finally, we synthesize emerging ILC-targeted therapeutic strategies and future research directions, proposing that a nuanced understanding of ILC biology is essential for developing novel immunotherapies aimed at restoring immune homeostasis in human diseases.

Keywords

diseases / homeostasis / immunotherapy / innate lymphoid cells / sepsis

References

[1] E. Vivier, D. Artis, M. Colonna, et al., “Innate Lymphoid Cells: 10 Years On,” Cell 174 (2018): 1054–1066.

[2] G. F. Sonnenberg and M. R. Hepworth, “Functional Interactions Between Innate Lymphoid Cells and Adaptive Immunity,” Nature Reviews Immunology 19 (2019): 599–613.

[3] B. Zeng, S. Shi, G. Ashworth, C. Dong, J. Liu, and F. Xing, “ILC3 Function as a Double-Eddiseasesged Sword in Inflammatory Bowel,” Cell Death & Disease 10 (2019): 315.

[4] R. K. Srivastava, L. Sapra, A. Bhardwaj, P. K. Mishra, B. Verma, and Z. Baig, “Unravelling the Immunobiology of Innate Lymphoid Cells (ILCs): Implications in Health and Disease,” Cytokine & Growth Factor Reviews 74 (2023): 56–75.

[5] M. Singer, C. S. Deutschman, C. W. Seymour, et al., “The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3),” Jama 315 (2016): 801.

[6] W. Zhang, H. Jiang, G. Wu, et al., “The Pathogenesis and Potential Therapeutic Targets in Sepsis,” MedComm 4 (2023): e418.

[7] M. Theertha, S. Sanju, V. V. Priya, P. Jain, P. K. Varma, and U. Mony, “Innate Lymphoid Cells: Potent Early Mediators of the Host Immune Response During Sepsis,” Cellular & Molecular Immunology 17 (2020): 1114–1116.

[8] M. Ghaedi and F. Takei, “Innate Lymphoid Cell Development,” Journal of Allergy and Clinical Immunology 147 (2021): 1549–1560.

[9] C. S. N. Klose and D. Artis, “Innate Lymphoid Cells Control Signaling Circuits to Regulate Tissue-Specific Immunity,” Cell Research 30 (2020): 475–491.

[10] D. N. Kasal and A. Bendelac, “Multi-Transcription Factor Reporter Mice Delineate Early Precursors to the ILC and LTi Lineages,” Journal of Experimental Medicine 218 (2021): e20200487.

[11] G. Gasteiger, X. Fan, S. Dikiy, S. Y. Lee, and A. Y. Rudensky, “Tissue Residency of Innate Lymphoid Cells in Lymphoid and Nonlymphoid Organs,” Science 350 (2015): 981–985.

[12] S. B. Bennstein, J. Klumb, T. Niehues, and M. Uhrberg, “Circulating Innate Lymphoid Cells (ILCs) in Healthy Children: Reference Values for Evaluation of Treatment in Immunocompromised Pediatric Patients,” Journal of Clinical Immunology 42 (2022): 1405–1408.

[13] S. B. Bennstein and M. Uhrberg, “Circulating Innate Lymphoid Cells (cILCs): Unconventional Lymphocytes With Hidden Talents,” Journal of Allergy and Clinical Immunology 154 (2024): 523–536.

[14] Q. Liu, J. H. Lee, H. M. Kang, and C. H. Kim, “Identification of the Niche and Mobilization Mechanism for Tissue-Protective Multipotential Bone Marrow ILC Progenitors,” Science Advances 8 (2022): eabq1551.

[15] F. Wang, Y. Cui, D. He, L. Gong, and H. Liang, “Natural Killer Cells in Sepsis: Friends or Foes?,” Frontiers in immunology 14 (2023): 1101918.

[16] A. P. McFarland, A. Yalin, S.-Y. Wang, et al., “Multi-Tissue Single-Cell Analysis Deconstructs the Complex Programs of Mouse Natural Killer and Type 1 Innate Lymphoid Cells in Tissues and Circulation,” Immunity 54 (2021): 1320–1337.e4.

[17] N. Lopes, J. Galluso, B. Escalière, S. Carpentier, Y. M. Kerdiles, and E. Vivier, “Tissue-Specific Transcriptional Profiles and Heterogeneity of Natural Killer Cells and Group 1 Innate Lymphoid Cells,” Cell Reports Medicine 3 (2022): 100812.

[18] K. Yomogida, T. M. Bigley, T. Trsan, et al., “Hobit Confers Tissue-Dependent Programs to Type 1 Innate Lymphoid Cells,” Proceedings National Academy of Science of the United States of America 118 (2021): e2117965118.

[19] N. Jaeger, A. U. Antonova, D. Kreisel, et al., “Diversity of Group 1 Innate Lymphoid Cells in Human Tissues,” Nature Immunology 25 (2024): 1460–1473.

[20] H. Spits, J. H. Bernink, and L. Lanier, “NK Cells and Type 1 Innate Lymphoid Cells: Partners in Host Defense,” Nature Immunology 17 (2016): 758–764.

[21] C. Friedrich, R. Taggenbrock, and R. Doucet-Ladevèze, “Effector Differentiation Downstream of Lineage Commitment in ILC1s Is Driven by Hobit Across Tissues,” Nature Immunology 22 (2021): 1256–1267.

[22] C. Di Censo, M. Marotel, I. Mattiola, et al., “Granzyme A and CD160 Expression Delineates ILC1 With Graded Functions in the Mouse Liver,” European Journal of Immunology 51 (2021): 2568–2575.

[23] I. Meininger, A. Carrasco, A. Rao, T. Soini, E. Kokkinou, and J. Mjösberg, “Tissue-Specific Features of Innate Lymphoid Cells,” Trends in Immunology 41 (2020): 902–917.

[24] Y. Zhou, Z. Yu, and Y. Lu, “To Explore the Influencing Factors of Clinical Failure of Anti-Tumor Necrosis Factor-α (TNF-α) Therapy in Sepsis,” Life Sciences 369 (2025): 123556.

[25] X. Fu and Y. Wang, “Interferon-γ Regulates Immunosuppression in Septic Mice by Promoting the Warburg Effect Through the PI3K/AKT/mTOR Pathway,” Molecular Medicine 29 (2023): 95.

[26] L. F. K. Uhl, H. Cai, S. L. Oram, et al., “Interferon-γ Couples CD8+ T Cell Avidity and Differentiation During Infection,” Nature Communications 14 (2023): 6727.

[27] J. Steffen, S. Ehrentraut, U. Bank, et al., “Type 1 Innate Lymphoid Cells Regulate the Onset of Toxoplasma Gondii-Induced Neuroinflammation,” Cell Reports 38 (2022): 110564.

[28] J.-H. Schroeder, J. K. Howard, and G. M. Lord, “Transcription Factor-Driven Regulation of ILC1 and ILC3,” Trends in Immunology 43 (2022): 564–579.

[29] J. Carvelli, C. Piperoglou, J. Bourenne, et al., “Imbalance of Circulating Innate Lymphoid Cell Subpopulations in Patients With Septic Shock,” Frontiers in immunology 10 (2019): 2179.

[30] D. Cruz-Zárate, G. L. Cabrera-Rivera, and B. P. Ruiz-Sánchez, “Innate Lymphoid Cells Have Decreased HLA-DR Expression but Retain Their Responsiveness to TLR Ligands During Sepsis,” The Journal of Immunology 201 (2018): 3401–3410.

[31] M. Zhao, F. Shao, D. Yu, et al., “Maturation and Specialization of Group 2 Innate Lymphoid Cells Through the Lung-Gut Axis,” Nature Communications 13 (2022): 7600.

[32] M. Qin, Y. Fang, Q. Zheng, et al., “Tissue Microenvironment Induces Tissue Specificity of ILC2,” Cell Death Discovery 10 (2024): 324.

[33] C. S. N. Klose and D. Artis, “Innate Lymphoid Cells as Regulators of Immunity, Inflammation and Tissue Homeostasis,” Nature Immunology 17 (2016): 765–774.

[34] C. A. Akdis, P. D. Arkwright, M.-C. Brüggen, et al., “Type 2 Immunity in the Skin and Lungs,” Allergy 75 (2020): 1582–1605.

[35] C. L.-P. Thio, A. C.-Y. Lai, Y.-T. Ting, P.-Y. Chi, and Y.-J. Chang, “The Ketone Body β-Hydroxybutyrate Mitigates ILC2-Driven Airway Inflammation by Regulating Mast Cell Function,” Cell Reports 40 (2022): 111437.

[36] I. Ogulur, Y. Mitamura, D. Yazici, et al., “Type 2 Immunity in Allergic Diseases,” Cellular & Molecular Immunology 22 (2025): 211–242.

[37] C. Symowski and D. Voehringer, “Interactions Between Innate Lymphoid Cells and Cells of the Innate and Adaptive Immune System,” Frontiers in Immunology 8 (2017): 1422.

[38] A. M. Tsou, H. Yano, C. N. Parkhurst, et al., “Neuropeptide Regulation of Non-Redundant ILC2 Responses at Barrier Surfaces,” Nature 611 (2022): 787–793.

[39] J. Stockis, T. Yip, J. Moreno-Vicente, et al., “Cross-Talk Between ILC2 and Gata3^high T_regs Locally Constrains Adaptive Type 2 Immunity,” Science Immunology 9 (2024): eadl1903.

[40] Y. Akama, E. J. Park, N. Satoh-Takayama, et al., “Sepsis Induces Deregulation of IL-13 Production and PD-1 Expression in Lung Group 2 Innate Lymphoid Cells,” Shock (Augusta, Ga) 55 (2021): 357–370.

[41] Y. Xu, R. Zhou, Y. Yang, et al., “Discovery of ILC2 Extracellular Traps and ILC2 ETosis : A Novel Feature of Group 2 Innate Lymphoid Cells,” Allergy 79 (2024): 2283–2286.

[42] Y. Yang, Y. Li, Y. Xu, et al., “Group 2 Innate Lymphoid Cells Can Engulf and Destroy Bacteria,” Cellular & Molecular Immunology 18 (2021): 2569–2571.

[43] P. A. Krishack, T. J. Louviere, T. S. Decker, et al., “Protection Against Staphylococcus Aureus Bacteremia-Induced Mortality Depends on ILC2s and Eosinophils,” JCI Insight 4, no. 6 (2019): e124168, https://doi.org/10.1172/jci.insight.124168.

[44] T. T. Chun, C.-S. Chung, E. A. Fallon, et al., “Group 2 Innate Lymphoid Cells (ILC2s) Are Key Mediators of the Inflammatory Response in Polymicrobial Sepsis,” The American Journal of Pathology 188 (2018): 2097–2108.

[45] D. C. Nascimento, P. H. Melo, A. R. Piñeros, et al., “IL-33 Contributes to Sepsis-Induced Long-Term Immunosuppression by Expanding the Regulatory T Cell Population,” Nature Communications 8 (2017): 14919.

[46] W. Wang, N. Li, and X. Guo, “The Crosstalk Between ILC3s and Adaptive Immunity in Diseases,” The FEBS Journal 291, no. 18 (2023): 3965–3977.

[47] C. Zhong, M. Zheng, and J. Zhu, “Lymphoid Tissue Inducer—A Divergent Member of the ILC Family,” Cytokine & Growth Factor Reviews 42 (2018): 5–12.

[48] S. Guia and E. Narni-Mancinelli, “Helper-Like Innate Lymphoid Cells in Humans and Mice,” Trends in Immunology 41 (2020): 436–452.

[49] L. C. Rankin, J. R. Groom, M. Chopin, et al., “The Transcription Factor T-Bet Is Essential for the Development of NKp46+ Innate Lymphocytes via the Notch Pathway,” Nature Immunology 14 (2013): 389–395.

[50] S. M. Bal, K. Golebski, and H. Spits, “Plasticity of Innate Lymphoid Cell Subsets,” Nature Reviews Immunology 20 (2020): 552–565.

[51] S. B. Bennstein, S. Weinhold, Ö. Degistirici, et al., “Efficient in Vitro Generation of IL-22-Secreting ILC3 From CD34+ Hematopoietic Progenitors in a,” Human Mesenchymal Stem Cell Niche Front Immunol 12 (2021): 797432.

[52] V. Horn and G. F. Sonnenberg, “Group 3 Innate Lymphoid Cells in Intestinal Health and Disease,” Nature Reviews Gastroenterology & Hepatology 21 (2024): 428–443.

[53] L. Zhou, W. Zhou, A. M. Joseph, et al., “Group 3 Innate Lymphoid Cells Produce the Growth Factor HB-EGF to Protect the Intestine From TNF-Mediated Inflammation,” Nature Immunology 23 (2022): 251–261.

[54] L. Patnaude, M. Mayo, R. Mario, et al., “Mechanisms and Regulation of IL-22-Mediated Intestinal Epithelial Homeostasis and Repair,” Life Sciences 271 (2021): 119195.

[55] T. Brabec, M. Vobořil, D. Schierová, et al., “IL-17-Driven Induction of Paneth Cell Antimicrobial Functions Protects the Host From Microbiota Dysbiosis and Inflammation in the Ileum,” Mucosal Immunology 16 (2023): 373–385.

[56] K. J. Cavagnero, F. Li, and T. Dokoshi, “CXCL12+ Dermal Fibroblasts Promote Neutrophil Recruitment and Host Defense by Recognition of IL-17,” Journal of Experimental Medicine 221 (2024): e20231425.

[57] H. S. Deshmukh, Y. Liu, and O. R. Menkiti, “The Microbiota Regulates Neutrophil Homeostasis and Host Resistance to Escherichia Coli K1 Sepsis in Neonatal Mice,” Nature Medicine 20 (2014): 524–530.

[58] F. Deng, J.-J. Hu, and Z.-B. Lin, “Gut Microbe-Derived Milnacipran Enhances Tolerance to Gut Ischemia/Reperfusion Injury,” Cell Reports Medicine 4 (2023): 100979.

[59] R. Muir, M. Osbourn, A. V. Dubois, et al., “Innate Lymphoid Cells Are the Predominant Source of IL-17A During the Early Pathogenesis of Acute Respiratory Distress Syndrome,” American Journal of Respiratory and Critical Care Medicine 193 (2016): 407–416.

[60] S. Wang, P. Xia, Y. Chen, et al., “Regulatory Innate Lymphoid Cells Control Innate Intestinal Inflammation,” Cell 171 (2017): 201–216.e18.

[61] Q. Cao, R. Wang, Y. Wang, et al., “Regulatory Innate Lymphoid Cells Suppress Innate Immunity and Reduce Renal Ischemia/Reperfusion Injury,” Kidney International 97 (2020): 130–142.

[62] J. K. Bando, S. Gilfillan, B. Di Luccia, et al., “ILC2s are the Predominant Source of Intestinal ILC-Derived IL-10,” Journal of Experimental Medicine 217 (2020): e20191520.

[63] C. M. Thomas and R. S. Peebles, “Development and Function of Regulatory Innate Lymphoid Cells,” Frontiers in immunology 13 (2022): 1014774.

[64] M. H. O'Connor, R. Muir, and M. Chakhtoura, “A Follicular Regulatory Innate Lymphoid Cell Population Impairs Interactions Between Germinal Center Tfh and B Cells,” Communications Biology 4 (2021): 563.

[65] J. H. Bernink, L. Krabbendam, K. Germar, et al., “Interleukin-12 and -23 Control Plasticity of CD127+ Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria,” Immunity 43 (2015): 146–160.

[66] C. S. N. Klose, E. A. Kiss, V. Schwierzeck, et al., “A T-Bet Gradient Controls the Fate and Function of CCR6−RORγt+ Innate Lymphoid Cells,” Nature 494 (2013): 261–265.

[67] R. Fiancette, C. M. Finlay, C. Willis, et al., “Reciprocal Transcription Factor Networks Govern Tissue-Resident ILC3 Subset Function and Identity,” Nature Immunology 22 (2021): 1245–1255.

[68] A. A. Korchagina, E. Koroleva, and A. V. Tumanov, “Innate Lymphoid Cell Plasticity in Mucosal Infections,” Microorganisms 11 (2023): 461.

[69] T. R. McCulloch, G. R. Rossi, J. Schreuder, G. T. Belz, T. J. Wells, and F. Souza-Fonseca-Guimaraes, “CIS and TGF -β Regulatory Pathways Influence Immunity to Bacterial Infection,” Immunology 167 (2022): 54–63.

[70] E. Park, S. Patel, Q. Wang, et al., “Toxoplasma Gondii Infection Drives Conversion of NK Cells Into ILC1-Like Cells,” Elife 8 (2019): e47605.

[71] A. Raykova, P. Carrega, F. M. Lehmann, et al., “Interleukins 12 and 15 Induce Cytotoxicity and Early NK-Cell Differentiation in Type 3 Innate Lymphoid Cells,” Blood Advances 1 (2017): 2679–2691.

[72] C. Viant, L. C. Rankin, M. J. H. Girard-Madoux, et al., “Transforming Growth Factor–β and Notch Ligands Act as Opposing Environmental Cues in Regulating the Plasticity of Type 3 Innate Lymphoid Cells,” Science signaling 9, no. 426 (2016): ra46.

[73] A. Fuchs, S. Ghosh, S.-W. Chang, G. V. Bochicchio, and I. R. Turnbull, “Pseudomonas Aeruginosa Pneumonia Causes a Loss of Type-3 and an Increase in Type-1 Innate Lymphoid Cells in the Gut,” Journal of Surgical Research 265 (2021): 212–222.

[74] A. A. Korchagina, E. Koroleva, and A. V. Tumanov, “Innate Lymphoid Cells in Response to Intracellular Pathogens: Protection Versus Immunopathology,” Frontiers in Cellular and Infection Microbiology 11 (2021): 775554.

[75] J. S. Silver, J. Kearley, A. M. Copenhaver, et al., “Inflammatory Triggers Associated With Exacerbations of COPD Orchestrate Plasticity of Group 2 Innate Lymphoid Cells in the Lungs,” Nature Immunology 17 (2016): 626–635.

[76] Y. Huang, L. Guo, J. Qiu, et al., “IL-25-Responsive, Lineage-Negative KLRG1hi Cells Are Multipotential ‘Inflammatory’ Type 2 Innate Lymphoid Cells,” Nature Immunology 16 (2015): 161–169.

[77] K. Golebski, X. R. Ros, M. Nagasawa, et al., “IL-1β, IL-23, and TGF-β Drive Plasticity of Human ILC2s Towards IL-17-Producing ILCs in Nasal Inflammation,” Nature Communications 10 (2019): 2162.

[78] C. R. Seehus, A. Kadavallore, B. D. L. Torre, et al., “Alternative Activation Generates IL-10 Producing Type 2 Innate Lymphoid Cells,” Nature Communications 8 (2017): 1900.

[79] E. Howard, G. Lewis, L. Galle-Treger, et al., “IL-10 Production by ILC2s Requires Blimp-1 and cMaf, Modulates Cellular Metabolism, and Ameliorates Airway Hyperreactivity,” Journal of Allergy and Clinical Immunology 147 (2021): 1281–1295.e5.

[80] H. Morita, T. Kubo, B. Rückert, et al., “Induction of Human Regulatory Innate Lymphoid Cells From Group 2 Innate Lymphoid Cells by Retinoic Acid,” Journal of Allergy and Clinical Immunology 143 (2019): 2190–2201.e9.

[81] M. A. Akamatsu, J. T. De Castro, C. Y. Takano, and P. L. Ho, “Off Balance: Interferons in COVID-19 Lung Infections,” EBioMedicine 73 (2021): 103642.

[82] O.-E. Weizman, N. M. Adams, I. S. Schuster, et al., “ILC1 Confer Early Host Protection at Initial Sites of Viral Infection,” Cell 171 (2017): 795–808.e12.

[83] A. H. López-Yglesias, E. Burger, E. Camanzo, et al., “T-Bet-Dependent ILC1- and NK Cell-Derived IFN-γ Mediates cDC1-Dependent Host Resistance Against Toxoplasma Gondii,” PLOS Pathogens 17 (2021): e1008299.

[84] J. P. Shannon, S. M. Vrba, and G. V. Reynoso, “Group 1 Innate Lymphoid-Cell-Derived Interferon-γ Maintains Anti-Viral Vigilance in the Mucosal Epithelium,” Immunity 54 (2021): 276–290.e5.

[85] T. Asahi, S. Abe, G. Cui, et al., “Liver Type 1 Innate Lymphoid Cells Lacking IL-7 Receptor Are a Native Killer Cell Subset Fostered by Parenchymal Niches,” eLife 12 (2023): e84209.

[86] C. Schneider, C. E. O'Leary, and J. Von Moltke, “A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling,” Cell 174 (2018): 271–284.e14.

[87] X. Feng, T. Andersson, P. Flüchter, et al., “Tuft Cell IL-17RB Restrains IL-25 Bioavailability and Reveals Context-Dependent ILC2 Hypoproliferation,” Nature Immunology 26 (2025): 567–581.

[88] J. U. Mayer, K. L. Hilligan, J. S. Chandler, et al., “Homeostatic IL-13 in Healthy Skin Directs Dendritic Cell Differentiation to Promote TH2 and Inhibit TH17 Cell Polarization,” Nature Immunology 22 (2021): 1538–1550.

[89] M. Verma, U. I. Can, and R. L. Reinhardt, “ILC2 Diversity, Location, and Function in Pulmonary Disease,” Immunological Reviews 332 (2025): e70036.

[90] U. I. Can, S. E. Stenske, M. D. Rosenbaum, and R. L. Reinhardt, “Rapid Group-2 Innate Lymphoid Cell Mobilization From the Intestine Aids in Early Lung Defense and Repair,” Cell Reports 44 (2025): 115868.

[91] C. Chu, C. N. Parkhurst, W. Zhang, et al., “The ChAT-Acetylcholine Pathway Promotes Group 2 Innate Lymphoid Cell Responses and Anti-Helminth Immunity,” Science Immunology 6 (2021): eabe3218.

[92] S. Moriyama, J. R. Brestoff, A.-L. Flamar, et al., “β₂ -Adrenergic Receptor–Mediated Negative Regulation of Group 2 Innate Lymphoid Cell Responses,” Science 359 (2018): 1056–1061.

[93] Y. Cao, Y. Li, X. Wang, et al., “Dopamine Inhibits Group 2 Innate Lymphoid Cell-Driven Allergic Lung Inflammation by Dampening Mitochondrial Activity,” Immunity 56 (2023): 320–335.e9.

[94] L. P. Araujo, M. Edwards, K. Irie, et al., “Context-Dependent Role of Group 3 Innate Lymphoid Cells in Mucosal Protection,” Science Immunology 9 (2024): eade7530.

[95] S. L. Tai, F. Wong, K. Burrows, et al., “Group 3 Innate Lymphoid Cell-Derived CSF2 Tunes Homeostasis of Tissue Macrophages and Neutrophils,” Mucosal Immunology 18 (2025): 1450–1461.

[96] A. Jarade, Z. Garcia, and S. Marie, “Inflammation Triggers ILC3 Patrolling of the Intestinal Barrier,” Nature Immunology 23 (2022): 1317–1323.

[97] M. R. Hepworth, L. A. Monticelli, T. C. Fung, et al., “Innate Lymphoid Cells Regulate CD4+ T-Cell Responses to Intestinal Commensal Bacteria,” Nature 498 (2013): 113–117.

[98] M. Lyu, H. Suzuki, L. Kang, et al., “ILC3s Select Microbiota-Specific Regulatory T Cells to Establish Tolerance in the Gut,” Nature 610 (2022): 744–751.

[99] X. Gao, X. Shen, Q. Xu, et al., “The Transcription Factor IRF4 Regulates the Homeostasis and Function of Intestinal ILC3s,” iScience 28 (2025): 112800.

[100] X. Wu, A. Khatun, M. Y. Kasmani, et al., “Group 3 Innate Lymphoid Cells Require BATF to Regulate Gut Homeostasis in Mice,” Journal of Experimental Medicine 219 (2022): e20211861.

[101] L. Zhou, C. Chu, F. Teng, et al., “Innate Lymphoid Cells Support Regulatory T Cells in the Intestine Through Interleukin-2,” Nature 568 (2019): 405–409.

[102] S. A. Van De Pavert, “Layered Origins of Lymphoid Tissue Inducer Cells,” Immunological Reviews 315 (2023): 71–78.

[103] N. H. Ruddle, “From Lymphotoxin to Tertiary Lymphoid Structures and Beyond,” Immunological Reviews 335 (2025): e70062.

[104] C. Stehle, T. Rückert, R. Fiancette, et al., “T-Bet and RORα Control Lymph Node Formation by Regulating Embryonic Innate Lymphoid Cell Differentiation,” Nature Immunology 22 (2021): 1231–1244.

[105] T. Wu, S. Chen, X. Zhu, et al., “Dynamic Regulation of Innate Lymphoid Cell Development During Ontogeny,” Mucosal Immunology 17 (2024): 1285–1300.

[106] Y. Zhang, Z. Zhou, and Z. Zhang, “Lentinan Mitigates Ulcerative Colitis via the IL-22 Pathway to Repair the Compromised Mucosal Barrier and Enhance Antimicrobial Defense,” International Journal of Biological Macromolecules 307 (2025): 141784.

[107] H.-Y. Chiang, H.-H. Lu, J. N. Sudhakar, et al., “IL-22 Initiates an IL-18-Dependent Epithelial Response Circuit to Enforce Intestinal Host Defence,” Nature Communications 13 (2022): 874.

[108] Y. Sun, S. Huang, M. Li, et al., “Maternal High-Fat Diet Disrupts Intestinal Mucus Barrier of Offspring by Regulating Gut Immune Receptor LRRC19,” Communications Biology 8 (2025): 420.

[109] W. Wang, N. Li, H. Xu, et al., “ILC3s Regulate the Gut Microbiota via Host Intestinal Galactosylation to Limit Pathogen Infection in Mice,” Nature Microbiology 10 (2025): 654–666.

[110] C. Seillet, K. Luong, J. Tellier, et al., “The Neuropeptide VIP Confers Anticipatory Mucosal Immunity by Regulating ILC3 Activity,” Nature Immunology 21 (2020): 168–177.

[111] M. Pascal, A. Kazakov, G. Chevalier, et al., “The Neuropeptide VIP Potentiates Intestinal Innate Type 2 and Type 3 Immunity in Response to Feeding,” Mucosal Immunology 15 (2022): 629–641.

[112] M. Romera-Hernández, P. Aparicio-Domingo, N. Papazian, et al., “Yap1-Driven Intestinal Repair Is Controlled by Group 3 Innate Lymphoid Cells,” Cell Reports 30 (2020): 37–45.e3.

[113] M. J. Uddin, B. Thompson, and J. L. Leslie, “Investigating the Impact of Antibiotic-Induced Dysbiosis on Protection From Clostridium Difficile Colitis by Mouse Colonic Innate Lymphoid Cells,” MBio 15 (2024): e03338–23.

[114] X. Wu, M. Y. Kasmani, S. Zheng, et al., “BATF Promotes Group 2 Innate Lymphoid Cell–mediated Lung Tissue Protection During Acute Respiratory Virus Infection,” Science Immunology 7 (2022): eabc9934.

[115] G. Liu, H. Huang, Y. Wang, et al., “ILC2 Instructs Neural Stem and Progenitor Cells to Potentiate Neurorepair After Stroke,” Neuron 113 (2025): 1741–1757.e7.

[116] W.-Y. Chen, Y.-H. Wu, T.-H. Tsai, et al., “Group 2 Innate Lymphoid Cells Contribute to IL-33-Mediated Alleviation of Cardiac Fibrosis,” Theranostics 11 (2021): 2594–2611.

[117] A. E. Russi, P. Shivakumar, Z. Luo, and J. A. Bezerra, “Plasticity Between Type 2 Innate Lymphoid Cell Subsets and Amphiregulin Expression Regulates Epithelial Repair in Biliary Atresia,” Hepatology 78 (2023): 1035–1049.

[118] M. H. Wang, J. Liu, S. L. Li, M. Z. Zheng, R. Y. Qu, and M. Xiang, “Amphiregulin: A Potential Therapeutic Target for Tissue Fibrosis,” Trends in Pharmacological Sciences 46 (2025): 877–890.

[119] P. Sorkhdini, K. Klubock-Shukla, S. Sheth, et al., “Type 2 Innate Immunity Promotes the Development of Pulmonary Fibrosis in Hermansky-Pudlak Syndrome,” JCI Insight 9 (2024): e178381.

[120] J. Sun, Y. Zhang, Q. Zhang, et al., “Metabolic Regulator LKB1 Controls Adipose Tissue ILC2 PD-1 Expression and Mitochondrial Homeostasis to Prevent Insulin Resistance,” Immunity 57 (2024): 1289–1305.e9.

[121] Y. Liu, Z. Liu, J. Liang, and C. Sun, “ILC2s Control Obesity by Regulating Energy Homeostasis and Browning of White Fat,” International Immunopharmacology 120 (2023): 110272.

[122] J. R. Brestoff, B. S. Kim, S. A. Saenz, et al., “Group 2 Innate Lymphoid Cells Promote Beiging of White Adipose Tissue and Limit Obesity,” Nature 519 (2015): 242–246.

[123] M.-W. Lee, J. I. Odegaard, L. Mukundan, et al., “Activated Type 2 Innate Lymphoid Cells Regulate Beige Fat Biogenesis,” Cell 160 (2015): 74–87.

[124] A. B. Molofsky, J. C. Nussbaum, H.-E. Liang, et al., “Innate Lymphoid Type 2 Cells Sustain Visceral Adipose Tissue Eosinophils and Alternatively Activated Macrophages,” Journal of Experimental Medicine 210 (2013): 535–549.

[125] F. Cardoso, R. G. J. Klein Wolterink, C. Godinho-Silva, et al., “Neuro-Mesenchymal Units Control ILC2 and Obesity via a Brain–adipose Circuit,” Nature 597 (2021): 410–414.

[126] M. Fujimoto, M. Yokoyama, M. Kiuchi, et al., “Liver Group 2 Innate Lymphoid Cells Regulate Blood Glucose Levels Through IL-13 Signaling and Suppression of Gluconeogenesis,” Nature Communications 13 (2022): 5408.

[127] E. Dalmas, F. M. Lehmann, E. Dror, et al., “Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin Secretion Through Myeloid Cell Retinoic Acid Production,” Immunity 47 (2017): 928–942.e7.

[128] M. Šestan, B. Raposo, M. Rendas, et al., “Neuronal-ILC2 Interactions Regulate Pancreatic Glucagon and Glucose Homeostasis,” Science 387 (2025): eadi3624.

[129] H. Sajiir, G. A. Ramm, G. A. Macdonald, M. A. McGuckin, J. B. Prins, and S. Z. Hasnain, “Harnessing IL-22 for Metabolic Health: Promise and Pitfalls,” Trends in Molecular Medicine 31 (2025): 574–584.

[130] M. Cecconi, L. Evans, M. Levy, and A. Rhodes, “Sepsis and Septic Shock,” The Lancet 392 (2018): 75–87.

[131] X. Chen, Y. Liu, Y. Gao, S. Shou, and Y. Chai, “The Roles of Macrophage Polarization in the Host Immune Response to Sepsis,” International Immunopharmacology 96 (2021): 107791.

[132] Z. He, X. Pan, K. Xie, et al., “The Effects of Fisetin on Gene Expression Profile and Cellular Metabolism in IFN-γ-Stimulated Macrophage Inflammation,” Antioxidants 14 (2025): 182.

[133] I. Ito, K. K. Bhopale, M. Kobayashi, C. C. Finnerty, D. N. Herndon, and F. Suzuki, “Lamina Propria Group 2 Innate Lymphoid Cells Impair the Antibacterial Defense of Burned Mice to Enterococcal Translocation,” Journal of Leukocyte Biology 102 (2017): 1451–1460.

[134] W. Liang, J. Li, C. Bai, et al., “Interleukin-5 Deletion Promotes Sepsis-Induced M1 Macrophage Differentiation, Deteriorates Cardiac Dysfunction, and Exacerbates Cardiac Injury via the NF-κB p65 Pathway in Mice,” Biofactors 46 (2020): 1006–1017.

[135] X. Zhong, J. Jin, and H. Zhang, “Group 2 Innate Lymphoid Cells Derived IL-9 Reduces Macrophage Apoptosis and Attenuates Acute Lung Injury in Sepsis,” Inflammation Research 74 (2025): 38.

[136] T. Castro-Dopico, A. Fleming, T. W. Dennison, et al., “GM-CSF Calibrates Macrophage Defense and Wound Healing Programs During Intestinal Infection and Inflammation,” Cell Reports 32 (2020): 107857.

[137] S. Zhang, J. Rautela, N. G. Bediaga, et al., “CIS Controls the Functional Polarization of GM-CSF-Derived Macrophages,” Cellular & Molecular Immunology 20 (2022): 65–79.

[138] H. Xu, J. Xu, and L. Xu, “Interleukin-33 Contributes to ILC 2 Activation and Early Inflammation-Associated Lung Injury During Abdominal Sepsis,” Immunology and Cell Biology 96 (2018): 935–947.

[139] Z. Rao, S. Liu, Z. Li, et al., “Alarmin-Loaded Extracellular Lipid Droplets Induce Airway Neutrophil Infiltration During Type 2 Inflammation,” Immunity 57 (2024): 2514–2529.e7.

[140] K. Matsuda, N. Ide, Y. Xu, A. Iijima, and A. Shibuya, “Type 1 Innate Lymphoid Cell–immature Neutrophil Axis Suppresses Acute Tissue Inflammation,” Nature Communications 16 (2025): 6574.

[141] J. L. Fachi, S. D. Oliveira, S. Gilfillan, et al., “NKp46⁺ ILC3s Promote Early Neutrophil Defense Against Clostridioides Difficile Infection Through GM-CSF Secretion,” Proceedings National Academy of Science USA 121 (2024): e2416182121.

[142] J. M. Felton, R. Duffin, C. T. Robb, et al., “Facilitation of IL-22 Production From Innate Lymphoid Cells by Prostaglandin E₂ Prevents Experimental Lung Neutrophilic Inflammation,” Thorax 73 (2018): 1081–1084.

[143] A. Eken, A. K. Singh, P. M. Treuting, and M. Oukka, “IL-23R+ Innate Lymphoid Cells Induce Colitis via Interleukin-22-Dependent Mechanism,” Mucosal Immunology 7 (2014): 143–154.

[144] X. Liu, L. Chen, W. Peng, et al., “Th17/Treg Balance: The Bloom and Wane in the Pathophysiology of Sepsis,” Frontiers in immunology 15 (2024): 1356869.

[145] A. B. Molofsky, F. Van Gool, H.-E. Liang, et al., “Interleukin-33 and Interferon-γ Counter-Regulate Group 2 Innate Lymphoid Cell Activation During Immune Perturbation,” Immunity 43 (2015): 161–174.

[146] W. Chen, D. Lai, Y. Li, et al., “Neuronal-Activated ILC2s Promote IL-17A Production in Lung Γδ T Cells During Sepsis,” Frontiers in immunology 12 (2021): 670676.

[147] A. Mortha, A. Chudnovskiy, D. Hashimoto, et al., “Microbiota-Dependent Crosstalk Between Macrophages and ILC3 Promotes Intestinal Homeostasis,” Science 343 (2014): 1249288.

[148] N. Von Burg, S. Chappaz, and A. Baerenwaldt, “Activated Group 3 Innate Lymphoid Cells Promote T-Cell–mediated Immune Responses,” Proceedings National Academy of Science USA 111 (2014): 12835–12840.

[149] Y. Sun, Y. Lu, X. Pan, C. Zhang, L. Wang, and L. Zhang, “Early B Lymphocyte Subsets in Blood Predict Prognosis in Sepsis,” Frontiers in immunology 15 (2024): 1437864.

[150] A. A. Kruglov, S. I. Grivennikov, D. V. Kuprash, et al., “Nonredundant Function of Soluble LTα₃ Produced by Innate Lymphoid Cells in Intestinal Homeostasis,” Science 342 (2013): 1243–1246.

[151] G. Magri, M. Miyajima, S. Bascones, et al., “Innate Lymphoid Cells Integrate Stromal and Immunological Signals to Enhance Antibody Production by Splenic Marginal Zone B Cells,” Nature Immunology 15 (2014): 354–364.

[152] Z. I. Komlósi, N. Kovács, W. Van De Veen, et al., “Human CD40 Ligand–expressing Type 3 Innate Lymphoid Cells Induce IL-10–producing Immature Transitional Regulatory B Cells,” Journal of Allergy and Clinical Immunology 142 (2018): 178–194.e11.

[153] K. F. Troch, M. O. Jakob, and P. M. Forster, “Group 2 Innate Lymphoid Cells Are a Non-Redundant Source of Interleukin-5 Required for Development and Function of Murine B1 Cells,” Nature Communications 15 (2024): 10566.

[154] C. Tan, B. Reilly, G. Ma, et al., “Neutrophils Disrupt B-1a Cell Homeostasis by Targeting Siglec-G to Exacerbate Sepsis,” Cellular & Molecular Immunology 21 (2024): 707–722.

[155] D. Lai, J. Tang, L. Chen, et al., “Group 2 Innate Lymphoid Cells Protect Lung Endothelial Cells From Pyroptosis in Sepsis,” Cell Death & Disease 9 (2018): 369.

[156] D. Lai, W. Chen, K. Zhang, et al., “GRK2 Regulates Group 2 Innate Lymphoid Cell Mobilization in Sepsis,” Molecular Medicine 28 (2022): 32.

[157] V. Cardoso, J. Chesné, H. Ribeiro, et al., “Neuronal Regulation of Type 2 Innate Lymphoid Cells via Neuromedin U,” Nature 549 (2017): 277–281.

[158] J. P. Hoffmann, J. K. Kolls, and J. E. McCombs, “Regulation and Function of ILC3s in Pulmonary Infections,” Frontiers in Immunology 12 (2021): 672523.

[159] T. Yuan, Q. Zhou, Y. Tian, Y. Ou, Y. Long, and Y. Tan, “Innate Lymphoid Cells and Infectious Diseases,” Innate Immune 30 (2024): 120–135.

[160] R. Mittal and C. M. Coopersmith, “Redefining the Gut as the Motor of Critical Illness,” Trends in Molecular Medicine 20 (2014): 214–223.

[161] F. Deng, J.-J. Hu, X. Yang, et al., “Gut Microbial Metabolite Pravastatin Attenuates Intestinal Ischemia/Reperfusion Injury Through Promoting IL-13 Release From Type II Innate Lymphoid Cells via IL−33/ST2 Signaling,” Frontiers in Immunology 12 (2021): 704836.

[162] J. Gray, K. Oehrle, G. Worthen, T. Alenghat, J. Whitsett, and H. Deshmukh, “Intestinal Commensal Bacteria Mediate Lung Mucosal Immunity and Promote Resistance of Newborn Mice to Infection,” Science Translational Medicine 9 (2017): eaaf9412.

[163] Y. Su, C. Feng, W. Ye, et al., “Exploring the Dynamic Responses of Group 3 Innate Lymphoid Cells at Different Times in Response to LPS Challenge,” International Immunopharmacology 148 (2025): 114162.

[164] Y. Huang, K. Mao, X. Chen, et al., “S1P-Dependent Interorgan Trafficking of Group 2 Innate Lymphoid Cells Supports Host Defense,” Science 359 (2018): 114–119.

[165] M. M. Miller, P. S. Patel, K. Bao, T. Danhorn, B. P. O'Connor, and R. L. Reinhardt, “BATF Acts as an Essential Regulator of IL-25–responsive Migratory ILC2 Cell Fate and Function,” Science Immunology 5 (2020): eaay3994.

[166] Q. Pu, P. Lin, P. Gao, et al., “Gut Microbiota Regulate Gut–Lung Axis Inflammatory Responses by Mediating ILC2 Compartmental Migration,” The Journal of Immunology 207 (2021): 257–267.

[167] Y. Deng, S. Wu, Y. Yang, et al., “Unique Phenotypes of Heart Resident Type 2 Innate Lymphoid Cells,” Frontiers in Immunology 11 (2020): 802.

[168] W. Bracamonte-Baran, G. Chen, X. Hou, et al., “Non-Cytotoxic Cardiac Innate Lymphoid Cells Are a Resident and Quiescent Type 2-Commited Population,” Frontiers in Immunology 10 (2019): 634.

[169] D. Fan and R. Wu, “Mechanisms of the Septic Heart: From Inflammatory Response to Myocardial Edema,” Journal of Molecular and Cellular Cardiology 195 (2024): 73–82.

[170] T. Kuroshima, S. Kawaguchi, and M. Okada, “Current Perspectives of Mitochondria in Sepsis-Induced Cardiomyopathy,” IJMS 25 (2024): 4710.

[171] T. Hong, S. Li, X. Guo, et al., “IL-13 Derived Type 2 Innate Lymphocytes Ameliorates Cardiomyocyte Apoptosis Through STAT3 Signaling Pathway,” Frontiers in Cell and Developmental Biology 9 (2021): 742662.

[172] X. Guo, T. Hong, S. Zhang, et al., “IL-13 Alleviates Cardiomyocyte Apoptosis by Improving Fatty Acid Oxidation in Mitochondria,” Frontiers in Cell and Developmental Biology 9 (2021): 736603.

[173] R. Shao, W. Liu, Y. Feng, et al., “LAMP2-FLOT2 Interaction Enhances Autophagosome-Lysosome Fusion to Protect the Septic Heart in Response to ILC2,” Autophagy 21, no. 9 (2025): 1888–1910.

[174] K. Fang, H. Chen, J. Xie, D. Sun, and L. Li, “Group 2 Innate Lymphocytes Protect the Balance Between Autophagy and Apoptosis in Cardiomyocytes During Sepsis-Induced Cardiac Injury,” Scientific Reports 14 (2024): 25011.

[175] S. Alvarez-Argote, S. J. Paddock, M. A. Flinn, et al., “IL-13 Promotes Functional Recovery After Myocardial Infarction via Direct Signaling to Macrophages,” JCI Insight 9 (2024): e172702.

[176] T. Liu, Z. Meng, J. Liu, et al., “Group 2 Innate Lymphoid Cells Protect Mouse Heart From Myocardial Infarction Injury via Interleukin 5, Eosinophils, and Dendritic Cells,” Cardiovascular Research 119 (2023): 1046–1061.

[177] X. Yu, S. A. Newland, T. X. Zhao, et al., “Innate Lymphoid Cells Promote Recovery of Ventricular Function After Myocardial Infarction,” Journal of the American College of Cardiology 78 (2021): 1127–1142.

[178] Y. Akama, E. J. Park, N. Satoh-Takayama, et al., “Roles of Programmed Death-1 and Muscle Innate Lymphoid Cell-Derived Interleukin 13 in Sepsis-Induced Intensive Care Unit-Acquired Weakness,” J Cachexia Sarcopenia Muscle 15 (2024): 1999–2012.

[179] P. Wang, Y. Zheng, J. Sun, et al., “Sepsis Induced Dysfunction of Liver Type 1 Innate Lymphoid Cells,” BMC Immunology [Electronic Resource] 25 (2024): 57.

[180] L. Quatrini, E. Wieduwild, S. Guia, et al., “Host Resistance to Endotoxic Shock Requires the Neuroendocrine Regulation of Group 1 Innate Lymphoid Cells,” Journal of Experimental Medicine 214 (2017): 3531–3541.

[181] N. Jacquelot, C. Seillet, E. Vivier, and G. T. Belz, “Innate Lymphoid Cells and Cancer,” Nature Immunology 23 (2022): 371–379.

[182] N. Pun and D. R. Withers, “Cellular Cosmetics: How Innate Lymphoid Cells Can Recontour the Tumour Microenvironment,” European Journal of Immunology 55 (2025): e70041.

[183] P. Yin, P. Cao, Y. Liang, C. Wang, and Y. Tian, “Unlocking the Power of Innate Lymphoid Cell Plasticity in the Tumor Microenvironment: A Revolutionary Pathway for Cancer Immunotherapy,” Biochimica et Biophysica Acta (BBA)—Reviews on Cancer 1880 (2025): 189430.

[184] L. Ducimetière, G. Lucchiari, G. Litscher, et al., “Conventional NK Cells and Tissue-Resident ILC1s Join Forces to Control Liver Metastasis,” Proceedings National Academy of Science USA 118 (2021): e2026271118.

[185] U. Y. Moreno-Nieves, J. K. Tay, S. Saumyaa, et al., “Landscape of Innate Lymphoid Cells in Human Head and Neck Cancer Reveals Divergent NK Cell States in the Tumor Microenvironment,” Proceedings National Academy of Science USA 118 (2021): e2101169118.

[186] E. R. Kansler, S. Dadi, C. Krishna, et al., “Cytotoxic Innate Lymphoid Cells Sense Cancer Cell-Expressed Interleukin-15 to Suppress Human and Murine Malignancies,” Nature Immunology 23 (2022): 904–915.

[187] B. G. Nixon, C. Chou, C. Krishna, et al., “Cytotoxic Granzyme C–expressing ILC1s Contribute to Antitumor Immunity and Neonatal Autoimmunity,” Science Immunology 7 (2022): eabi8642.

[188] R. Ma, Z. Li, H. Tang, et al., “NKp46 Enhances Type 1 Innate Lymphoid Cell Proliferation and Function and Anti-Acute Myeloid Leukemia Activity,” Nature Communications 16 (2025): 989.

[189] Y. Gao, F. Souza-Fonseca-Guimaraes, T. Bald, et al., “Tumor Immunoevasion by the Conversion of Effector NK Cells Into Type 1 Innate Lymphoid Cells,” Nature Immunology 18 (2017): 1004–1015.

[190] L. Rethacker, M. Roelens, C. Bejar, E. Maubec, H. Moins-Teisserenc, and A. Caignard, “Specific Patterns of Blood ILCs in Metastatic Melanoma Patients and Their Modulations in Response to Immunotherapy,” Cancers 13 (2021): 1446.

[191] M. J. Schuijs, S. Png, A. C. Richard, et al., “ILC2-Driven Innate Immune Checkpoint Mechanism Antagonizes NK Cell Antimetastatic Function in the Lung,” Nature Immunology 21 (2020): 998–1009.

[192] E. Jou, N. Rodriguez-Rodriguez, A.-C. F. Ferreira, et al., “An Innate IL-25–ILC2–MDSC Axis Creates a Cancer-Permissive Microenvironment for Apc Mutation–driven Intestinal Tumorigenesis,” Science Immunology 7 (2022): eabn0175.

[193] R. N. O'Keefe, A. L. E. Carli, and D. Baloyan, “A Tuft Cell—ILC2 Signaling Circuit Provides Therapeutic Targets to Inhibit Gastric Metaplasia and Tumor Development,” Nature Communications 14 (2023): 6872.

[194] D. C. Maresca, B. Romano, M. R. Ambrosio, F. Somma, and T. Wyss, “Circulating Innate Lymphoid Cells Are Dysregulated in Patients With Prostate Cancer,” Cellular & Molecular Biology Letters 30 (2025): 48.

[195] Y. Okuyama, A. Okajima, N. Sakamoto, et al., “IL-33-ILC2 Axis Promotes Anti-Tumor CD8+ T Cell Responses via OX40 Signaling,” Biochemical and Biophysical Research Communications 637 (2022): 9–16.

[196] N. Jacquelot, C. Seillet, M. Wang, et al., “Blockade of the Co-Inhibitory Molecule PD-1 Unleashes ILC2-Dependent Antitumor Immunity in Melanoma,” Nature Immunology 22 (2021): 851–864.

[197] J. Kim, S. G. Song, S. Park, et al., “Antigen Cross-Presentation by Type-2 Innate Lymphoid Cells Facilitates the Activation of Antitumor CD8+ T Cells,” Cancer Research 85 (2025): 2659–2678.

[198] I. Mattiola and A. Diefenbach, “Enabling Anti-Tumor Immunity by Unleashing ILC2,” Cell Research 30 (2020): 461–462.

[199] B. Heinrich, E. M. Gertz, A. A. Schäffer, et al., “The Tumour Microenvironment Shapes Innate Lymphoid Cells in Patients With Hepatocellular Carcinoma,” Gut 71 (2022): 1161–1175.

[200] I. Saranchova, C. W. Xia, S. Besoiu, et al., “A Novel Type-2 Innate Lymphoid Cell-Based Immunotherapy for Cancer,” Frontiers in immunology 15 (2024): 1317522.

[201] Z. Li, R. Ma, H. Tang, et al., “Therapeutic Application of Human Type 2 Innate Lymphoid Cells via Induction of Granzyme B-Mediated Tumor Cell Death,” Cell 187 (2024): 624–641.e23.

[202] J. Goc, M. Lv, N. J. Bessman, et al., “Dysregulation of ILC3s Unleashes Progression and Immunotherapy Resistance in Colon Cancer,” Cell 184 (2021): 5015–5030.e16.

[203] M. Bruchard, M. Geindreau, A. Perrichet, et al., “Recruitment and Activation of Type 3 Innate Lymphoid Cells Promote Antitumor Immune Responses,” Nature Immunology 23 (2022): 262–274.

[204] J.-J. Siegler, M. P. Correia, T. Hofman, et al., “Human ILC3 Exert TRAIL-Mediated Cytotoxicity Towards Cancer Cells,” Frontiers in Immunology 13 (2022): 742571.

[205] Y. Liu, Y. Song, D. Lin, et al., “NCR− Group 3 Innate Lymphoid Cells Orchestrate IL-23/IL-17 Axis to Promote Hepatocellular Carcinoma Development,” EBioMedicine 41 (2019): 333–344.

[206] C. Hu, B. Xu, and X. Wang, “Gut Microbiota–derived Short-Chain Fatty Acids Regulate Group 3 Innate Lymphoid Cells in HCC,” Hepatology 77 (2023): 48–64.

[207] K. M. Kaiser, J. Raabe, M. ToVinh, et al., “IL-17A-Producing NKp44(−) Group 3 Innate Lymphoid Cells Accumulate in Familial Adenomatous Polyposis Duodenal Tissue,” Nature Communications 16 (2025): 3873.

[208] A. Iwata, Y. Toda, H. Furuya, and H. Nakajima, “Group 2 Innate Lymphoid Cells in Human Asthma,” Allergology International 72 (2023): 194–200.

[209] C. L.-P. Thio, J.-S. Shao, C.-H. Luo, and Y.-J. Chang, “Decoding Innate Lymphoid Cells and Innate-Like Lymphocytes in Asthma: Pathways to Mechanisms and Therapies,” Journal of Biomedical Science 32 (2025): 48.

[210] C. L.-P. Thio and Y.-J. Chang, “The Modulation of Pulmonary Group 2 Innate Lymphoid Cell Function in Asthma: From Inflammatory Mediators to Environmental and Metabolic Factors,” Experimental & Molecular Medicine 55 (2023): 1872–1884.

[211] J. Dhariwal, A. Cameron, E. Wong, et al., “Pulmonary Innate Lymphoid Cell Responses During Rhinovirus-Induced Asthma Exacerbations in Vivo : A Clinical Trial,” American Journal of Respiratory and Critical Care Medicine 204 (2021): 1259–1273.

[212] S. Strickson, K. F. Houslay, V. A. Negri, et al., “Oxidised IL-33 Drives COPD Epithelial Pathogenesis via ST2-Independent RAGE/EGFR Signalling Complex,” European Respiratory Journal 62 (2023): 2202210.

[213] W. Wang, Y. Li, Z. Lv, et al., “Bronchial Allergen Challenge of Patients With Atopic Asthma Triggers an Alarmin (IL-33, TSLP, and IL-25) Response in the Airways Epithelium and Submucosa,” The Journal of Immunology 201 (2018): 2221–2231.

[214] S. G. Smith, R. Chen, and M. Kjarsgaard, “Increased Numbers of Activated Group 2 Innate Lymphoid Cells in the Airways of Patients With Severe Asthma and Persistent Airway Eosinophilia,” Journal of Allergy and Clinical Immunology 137 (2016): 75–86.e8.

[215] Y. Jia, X. Fang, and X. Zhu, “IL-13⁺ Type 2 Innate Lymphoid Cells Correlate With Asthma Control Status and Treatment Response,” American Journal of Respiratory Cell and Molecular Biology 55 (2016): 675–683.

[216] H. Gan, Z. Huang, Q. Pan, F. Ye, Z. Zhu, and B. Sun, “Recurrence of Acute Allergic Asthma Depends on the Role of ILC2 Driven by Il1rl1 Signaling,” Cell Communication and Signaling 23 (2025): 215.

[217] L. Wang, K. G. Netto, L. Zhou, et al., “Single-Cell Transcriptomic Analysis Reveals the Immune Landscape of Lung in Steroid-Resistant Asthma Exacerbation,” Proceedings National Academy of Science USA 118 (2021): e2005590118.

[218] J. Kim, J. Ham, H. R. Kang, Y.-S. Bae, T. Kim, and H. Y. Kim, “JAK3 Inhibitor Suppresses Multipotent ILC2s and Attenuates Steroid-Resistant Asthma,” Science Advances 9 (2023): eadi3770.

[219] C. Beuraud, V. Lombardi, S. Luce, et al., “CCR 10⁺ ILC 2s With ILC 1-Like Properties Exhibit a Protective Function in Severe Allergic Asthma,” Allergy 74 (2019): 933–943.

[220] F. Yang, X. Luo, W. Zhu, J. Li, Z. Zheng, and P. Zhu, “Dysregulation of Innate Lymphoid Cells in Patients With Active Rheumatoid Arthritis and Mice With Collagen-Induced Arthritis,” Mediators of Inflammation 2021 (2021): 1915068.

[221] I.-C. Kuo, J. Brassard, P. W. Zandstra, and K. M. McNagny, “Innate Lymphoid Cells in the Spotlight: From Biomarkers to Blueprint for Innovative Immunotherapy,” Frontiers in immunology 16 (2025): 1655730.

[222] A. S. Clottu, M. Humbel, N. Fluder, M. P. Karampetsou, and D. Comte, “Innate Lymphoid Cells in Autoimmune Diseases,” Frontiers in Immunology 12 (2022): 789788.

[223] A. Takaki-Kuwahara, Y. Arinobu, K. Miyawaki, et al., “CCR6+ Group 3 Innate Lymphoid Cells Accumulate in Inflamed Joints in Rheumatoid Arthritis and Produce Th17 Cytokines,” Arthritis Research & Therapy 21 (2019): 198.

[224] T. Wang, J. Rui, W. Shan, et al., “Imbalance of Th17, Treg, and Helper Innate Lymphoid Cell in the Peripheral Blood of Patients With Rheumatoid Arthritis,” Clinical Rheumatology 41 (2022): 3837–3849.

[225] X. Liu, L. Wu, S. Chen, et al., “Group 3 Innate Lymphoid Cells Promotes Th17 Cells Differentiation in Rheumatoid Arthritis,” Clinical and Experimental Rheumatology 42, no. 11 (2024): 2183–2193, https://doi.org/10.55563/clinexprheumatol/ktbiqc.

[226] M. Lo Pizzo, L. La Barbera, and C. Rizzo, “JAK/STAT Inhibition Modifies the ILC1 Immune Response in Patients With Rheumatoid Arthritis,” Clinical and Experimental Rheumatology 42, no. 3 (2023): 593–600, https://doi.org/10.55563/clinexprheumatol/hhcnmt.

[227] A. Arra, K. Vogel, I. Han, et al., “PD1+ Innate Lymphoid Cells 3 Predict JAK-Dependent Inflammation in Rheumatoid Arthritis,” Journal of Autoimmunity 154 (2025): 103424.

[228] J. Li, A. L. Doty, Y. Tang, et al., “Enrichment of IL-17A+IFN-γ+ and IL-22+IFN-γ+ T Cell Subsets Is Associated With Reduction of NKp44+ILC3s in the Terminal Ileum of Crohn's Disease Patients,” Clinical and Experimental Immunology 190 (2017): 143–153.

[229] B. Creyns, I. Jacobs, B. Verstockt, et al., “Biological Therapy in Inflammatory Bowel Disease Patients Partly Restores Intestinal Innate Lymphoid Cell Subtype Equilibrium,” Frontiers in immunology 11 (2020): 1847.

[230] M. Forkel, S. Van Tol, C. Höög, J. Michaëlsson, S. Almer, and J. Mjösberg, “Distinct Alterations in the Composition of Mucosal Innate Lymphoid Cells in Newly Diagnosed and Established Crohn's Disease and Ulcerative Colitis,” Journal of Crohn's and Colitis 13 (2019): 67–78.

[231] J. Hao, C. Liu, Z. Gu, X. Yang, X. Lan, and X. Guo, “Dysregulation of Wnt/β-Catenin Signaling Contributes to Intestinal Inflammation Through Regulation of Group 3 Innate Lymphoid Cells,” Nature Communications 15 (2024): 2820.

[232] X. Li, J. He, X. Gao, et al., “GPX4 Restricts Ferroptosis of NKp46+ILC3s to Control Intestinal Inflammation,” Cell Death & Disease 15 (2024): 687.

[233] A. Ahmed, A. M. Joseph, J. Zhou, et al., “CTLA-4-Expressing ILC3s Restrain Interleukin-23-Mediated Inflammation,” Nature 630 (2024): 976–983.

[234] N. Powell, E. Pantazi, P. Pavlidis, et al., “Interleukin-22 Orchestrates a Pathological Endoplasmic Reticulum Stress Response Transcriptional Programme in Colonic Epithelial Cells,” Gut 69 (2020): 578–590.

[235] X. Zhao, J. Li, Y. Zhang, et al., “Elevated Nitric Oxide During Colitis Restrains GM-CSF Production in ILC3 Cells via Suppressing an AhR-Cyp4f13-NF-κB Axis,” Nature Communications 16 (2025): 5654.

[236] Q. Ye, S. Huang, Y. Wang, et al., “Wogonin Improves Colitis by Activating the AhR Pathway to Regulate the Plasticity of ILC3/ILC1,” Phytomedicine 128 (2024): 155425.

[237] J. Li, J. Jacobse, J. M. Pilat, et al., “Interleukin-10 Production by Innate Lymphoid Cells Restricts Intestinal Inflammation in Mice,” Mucosal Immunology 18 (2025): 643–655.

[238] H. Wang, L. Shen, X. Sun, et al., “Adipose Group 1 Innate Lymphoid Cells Promote Adipose Tissue Fibrosis and Diabetes in Obesity,” Nature Communications 10 (2019): 3254.

[239] T. E. O'Sullivan, M. Rapp, X. Fan, et al., “Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance,” Immunity 45 (2016): 428–441.

[240] P. Hou, Y. Yao, Q. Bai, et al., “Short Term High-Fat Diet Induced Liver ILC1 Differentiation Associated With the TLR9 Activation,” The Journal of Nutritional Biochemistry 136 (2025): 109810.

[241] L. Zhou, Q. Lin, and G. F. Sonnenberg, “Metabolic Control of Innate Lymphoid Cells in Health and Disease,” Nature Metabolism 4 (2022): 1650–1659.

[242] R. Liébana-García, M. Olivares, C. Francés-Cuesta, et al., “Intestinal Group 1 Innate Lymphoid Cells Drive Macrophage-Induced Inflammation and Endocrine Defects in Obesity and Promote Insulinemia,” Gut Microbes 15 (2023): 2181928.

[243] A. O. Cuff, F. Sillito, S. Dertschnig, et al., “The Obese Liver Environment Mediates Conversion of NK Cells to a Less Cytotoxic ILC1-Like Phenotype,” Frontiers in Immunology 10 (2019): 2180.

[244] S. Boulenouar, X. Michelet, D. Duquette, et al., “Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis Through Targeted Cytotoxicity,” Immunity 46 (2017): 273–286.

[245] T. Okamura, Y. Hashimoto, J. Mori, et al., “ILC2s Improve Glucose Metabolism Through the Control of Saturated Fatty Acid Absorption Within Visceral Fat,” Frontiers in Immunology 12 (2021): 669629.

[246] P. Shafiei-Jahani, B. P. Hurrell, L. Galle-Treger, et al., “DR3 Stimulation of Adipose Resident ILC2s Ameliorates Type 2 Diabetes Mellitus,” Nature Communications 11 (2020): 4718.

[247] L. Galle-Treger, I. Sankaranarayanan, B. P. Hurrell, et al., “Costimulation of Type-2 Innate Lymphoid Cells by GITR Promotes Effector Function and Ameliorates Type 2 Diabetes,” Nature Communications 10 (2019): 713.

[248] P. Shafiei-Jahani, S. Yan, M. H. Kazemi, et al., “CB2 Stimulation of Adipose Resident ILC2s Orchestrates Immune Balance and Ameliorates Type 2 Diabetes Mellitus,” Cell Reports 43 (2024): 114434.

[249] S. A. Newland, S. Mohanta, M. Clément, et al., “Type-2 Innate Lymphoid Cells Control the Development of Atherosclerosis in Mice,” Nature Communications 8 (2017): 15781.

[250] T. Sasaki, K. Moro, T. Kubota, et al., “Innate Lymphoid Cells in the Induction of Obesity,” Cell Reports 28 (2019): 202–217.e7.

[251] M. Hamaguchi, T. Okamura, T. Fukuda, et al., “Group 3 Innate Lymphoid Cells Protect Steatohepatitis From High-Fat Diet Induced Toxicity,” Frontiers in Immunology 12 (2021): 648754.

[252] H. H. Nguyen, J. Talbot, D. Li, V. Raghavan, and D. R. Littman, “Modulating Intestinal Neuroimmune VIPergic Signaling Attenuates the Reduction in ILC3-Derived IL-22 and Hepatic Steatosis in MASLD,” Hepatology Communications 8, no. 11 (2024): e0528.

[253] J. Leentjens, M. Kox, R. M. Koch, et al., “Reversal of Immunoparalysis in Humans in Vivo: A Double-Blind, Placebo-Controlled, Randomized Pilot Study,” American Journal of Respiratory and Critical Care Medicine 186 (2012): 838–845.

[254] E. M. Pinder, A. J. Rostron, T. P. Hellyer, et al., “Randomised Controlled Trial of GM-CSF in Critically Ill Patients With Impaired Neutrophil Phagocytosis,” Thorax 73 (2018): 918–925.

[255] Q. Zhang, N. Zhong, S. Dhooria, et al., “Dupilumab Efficacy and Safety in Patients With Persistent Asthma: Asia–Pacific Region,” Clin Experimental Allergy 55 (2025): 691–700.

[256] T. Nopsopon, G. Lassiter, M.-L. Chen, et al., “Comparative Efficacy of Tezepelumab to Mepolizumab, Benralizumab, and Dupilumab in Eosinophilic Asthma: A Bayesian Network Meta-Analysis,” Journal of Allergy and Clinical Immunology 151 (2023): 747–755.

[257] F. J. Blanco, R. Möricke, E. Dokoupilova, et al., “Secukinumab in Active Rheumatoid Arthritis: A Phase III Randomized, Double-Blind, Active Comparator– and Placebo-Controlled Study,” Arthritis & Rheumatology 69 (2017): 1144–1153.

[258] J. Li, J. Fan, L. Wu, et al., “Astragalus Regulates the Intestinal Immune Response During Sepsis by Mediating ILC3 Proliferation Through RORγt,” Heliyon 9 (2023): e17766.

[259] Y. Shindo, A. G. Fuchs, C. G. Davis, et al., “Interleukin 7 Immunotherapy Improves Host Immunity and Survival in a Two-Hit Model of Pseudomonas Aeruginosa Pneumonia,” Journal of Leukocyte Biology 101 (2017): 543–554.

[260] X. Niu, S. Daniel, D. Kumar, et al., “Transient Neonatal Antibiotic Exposure Increases Susceptibility to Late-Onset Sepsis Driven by Microbiota-Dependent Suppression of Type 3 Innate Lymphoid Cells,” Scientific Reports 10 (2020): 12974.

[261] D. Zhao, B. Yang, C. Ye, S. Zhang, X. Lv, and Q. Chen, “Enteral Nutrition Ameliorates the Symptoms of Crohn's Disease in Mice via Activating Special Pro-Resolving Mediators Through Innate Lymphoid Cells,” Innate Immune 27 (2021): 533–542.

[262] M. E. Wechsler, M. K. Ruddy, I. D. Pavord, et al., “Efficacy and Safety of Itepekimab in Patients With Moderate-To-Severe Asthma,” New England Journal of Medicine 385 (2021): 1656–1668.

[263] J.-F. Colombel, J. Wu, T. Kobayashi, et al., “Mirikizumab Impact on Disease Clearance in Patients With Moderately to Severely Active Ulcerative Colitis: Analysis of a Pre-Specified LUCENT Trial Endpoint,” Journal of Crohn's and Colitis 19 (2025): jjaf124.

[264] M. J. García, M. Rivero, A. Fernández-Clotet, et al., “Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data From the ENEIDA Registry,” Journal of Crohn's and Colitis 18 (2024): 65–74.

[265] T. Daix, A. Mathonnet, S. Brakenridge, et al., “Intravenously Administered Interleukin-7 to Reverse Lymphopenia in Patients With Septic Shock: A Double-Blind, Randomized, Placebo-Controlled Trial,” Ann Intensive Care 13 (2023): 17.

[266] D. Chaudhuri, A. M. Nei, B. Rochwerg, et al., “2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia,” Critical Care Medicine 52 (2024): e219–e233.

[267] Q. Liu, M. H. Kim, L. Friesen, and C. H. Kim, “BATF Regulates Innate Lymphoid Cell Hematopoiesis and Homeostasis,” Science Immunology 5 (2020): eaaz8154.

[268] E. Watanabe, O. Nishida, Y. Kakihana, et al., “Pharmacokinetics, Pharmacodynamics, and Safety of Nivolumab in Patients With Sepsis-Induced Immunosuppression: A Multicenter, Open-Label Phase 1/2 Study,” Shock (Augusta, Ga) 53 (2020): 686–694.

[269] R. S. Hotchkiss, E. Colston, S. Yende, et al., “Immune Checkpoint Inhibition in Sepsis: A Phase 1b Randomized Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Nivolumab,” Intensive Care Medicine 45 (2019): 1360–1371.

[270] J. Hrdý, A. Couturier-Maillard, D. Boutillier, et al., “Oral Supplementation With Selected Lactobacillus Acidophilus Triggers IL-17-Dependent Innate Defense Response, Activation of Innate Lymphoid Cells Type 3 and Improves Colitis,” Scientific Reports 12 (2022): 17591.

[271] J.-J. Hu, F. Deng, and Q.-S. Sun, “Time-Restricted Feeding Protects Against Septic Liver Injury by Reshaping Gut Microbiota and Metabolite 3-Hydroxybutyrate,” Gut Microbes 17 (2025): 2486515.

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