Research Advancements in the Interplay between T3 and Macrophages

Abstract

3,3′,5-Triiodo-L-thyronine (T3) is a key endocrine hormone in the human body that plays crucial roles in growth, development, metabolism, and immune function. Macrophages, the key regulatory cells within the immune system, exhibit marked “heterogeneity” and “plasticity”, with their phenotype and function subject to modulation by local environmental signals. The interplay between the endocrine and immune systems is well documented. Numerous studies have shown that T3 significantly target macrophages, highlighting them as key cellular components in this interaction. Through the regulation of macrophage function and phenotype, T3 influences immune function and tissue repair in the body. This review comprehensively summarizes the regulatory actions and mechanisms of T3 on macrophages, offering valuable insights into further research of the immunoregulatory effects of T3.

References

[1] Mendoza A, Hollenberg AN. New insights into thyroid hormone action. Pharmacol Ther, 2017, 173: 135-145

[2] Galton VA, Hernandez A. Thyroid Hormone Metabolism: A Historical Perspective. Thyroid, 2023, 33(1): 24-31

[3] Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev, 2014, 94(2): 355-382

[4] Gereben B, McAninch EA, Ribeiro MO, et al.. Scope and limitations of iodothyronine deiodinases in hypothyroidism. Nat Rev Endocrinol, 2015, 11(11): 642-652

[5] van der Spek AH, Fliers E, Boelen A. The classic pathways of thyroid hormone metabolism. Mol Cell Endocrinol, 2017, 458: 29-38

[6] Gauthier BR, Sola-García A, Cáliz-Molina M, et al.. Thyroid hormones in diabetes, cancer, and aging. Aging Cell, 2020, 19(11): e13260

[7] Zhang J, Lazar MA. The mechanism of action of thyroid hormones. Annu Rev Physiol, 2000, 62: 439-66

[8] Davis PJ, Mousa SA, Lin HY. Nongenomic Actions of Thyroid Hormone: The Integrin Component. Physiol Rev, 2021, 101(1): 319-352

[9] Senese R, Cioffi F, de Lange P, et al.. Thyroid: biological actions of ‘nonclassical’ thyroid hormones. J Endocrinol, 2014, 221(2): 1-12

[10] Lafuse WP, Wozniak DJ, Rajaram MVS. Role of Cardiac Macrophages on Cardiac Inflammation, Fibrosis and Tissue Repair. Cells, 2020, 10(1): 51

[11] Yang S, Zhao M, Jia S. Macrophage: Key player in the pathogenesis of autoimmune diseases. Front Immunol, 2023, 14: 1080310

[12] Barrett TJ. Macrophages in Atherosclerosis Regression. Arterioscler Thromb Vasc Biol, 2020, 40(1): 20-33

[13] Mehla K, Singh PK. Metabolic Regulation of Macrophage Polarization in Cancer. Trends Cancer, 2019, 5(12): 822-834

[14] Han H, Ge X, Komakula SSB, et al.. Macrophage-derived Osteopontin (SPP1) Protects From Nonalcoholic Steatohepatitis. Gastroenterology, 2023, 165(1): 201-217

[15] Jenkins SJ, Ruckerl D, Cook PC, et al.. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science, 2011, 332(6035): 1284-1288

[16] Varol C, Mildner A, Jung S. Macrophages: development and tissue specialization. Annu Rev Immunol, 2015, 33: 643-675

[17] Wendimu MY, Hooks SB. Microglia Phenotypes in Aging and Neurodegenerative Diseases. Cells, 2022, 11(13): 2091

[18] Remmerie A, Martens L, Thoné T, et al.. Osteopontin Expression Identifies a Subset of Recruited Macrophages Distinct from Kupffer Cells in the Fatty Liver. Immunity, 2020, 53(3): 641-657

[19] Ginhoux F, Guilliams M. Tissue-Resident Macrophage Ontogeny and Homeostasis. Immunity, 2016, 44(3): 439-449

[20] Lazarov T, Juarez-Carreño S, Cox N, et al.. Physiology and diseases of tissue-resident macrophages. Nature, 2023, 618(7966): 698-707

[21] Ginhoux F, Guilliams M. Tissue-Resident Macrophage Ontogeny and Homeostasis. Immunity, 2016, 44(3): 439-449

[22] Locati M, Curtale G, Mantovani A. Diversity, Mechanisms, and Significance of Macrophage Plasticity. Annu Rev Pathol, 2020, 15: 123-147

[23] Orecchioni M, Ghosheh Y, Pramod AB, et al.. Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively, Activated Macrophages. Front Immunol, 2019, 10: 1084

[24] Chen S, Saeed AFUH, Liu Q, et al.. Macrophages in immunoregulation and therapeutics. Signal Transduct Target Ther, 2023, 8(1): 207

[25] Kadomoto S, Izumi K, Mizokami A. Macrophage Polarity and Disease Control. Int J Mol Sci, 2021, 23(1): 144

[26] Knezevic E, Nenic K, Milanovic V, et al.. The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders. Cells, 2023, 12(23): 2726

[27] Montesinos MDM, Pellizas CG. Thyroid Hormone Action on Innate Immunity. Front Endocrinol (Lausanne), 2019, 10: 350

[28] Chakraborty B, Byemerwa J, Krebs T, et al.. Estrogen Receptor Signaling in the Immune System. Endocr Rev, 2023, 44(1): 117-141

[29] Mascanfroni I, Montesinos Mdel M, Susperreguy S, et al.. Control of dendritic cell maturation and function by triiodothyronine. FASEB J, 2008, 22(4): 1032-1042

[30] Magsino CH Jr Hamouda W, Ghanim H, et al.. Effect of triiodothyronine on reactive oxygen species generation by leukocytes, indices of oxidative damage, and antioxidant reserve. Metabolism, 2000, 49(6): 799-803

[31] Rubingh J, van der Spek A, Fliers E, et al.. The Role of Thyroid Hormone in the Innate and Adaptive Immune Response during Infection. Compr Physiol, 2020, 10(4): 1277-1287

[32] van der Spek AH, Surovtseva OV, Jim KK, et al.. Regulation of Intracellular Triiodothyronine Is Essential for Optimal Macrophage Function. Endocrinology, 2018, 159(5): 2241-2252

[33] van der Spek AH, Fliers E, Boelen A. Thyroid Hormone and Deiodination in Innate Immune Cells. Endocrinology, 2021, 162(1): bqaa200

[34] Yona S, Jung S. Monocytes: subsets, origins, fates and functions. Curr Opin Hematol, 2010, 17(1): 53-59

[35] Gentek R, Molawi K, Sieweke MH. Tissue macrophage identity and self-renewal. Immunol Rev, 2014, 262(1): 56-73

[36] Elchaninov A, Vishnyakova P, Menyailo E, et al.. An Eye on Kupffer Cells: Development, Phenotype and the Macrophage Niche. Int J Mol Sci, 2022, 23(17): 9868

[37] Wen Y, Lambrecht J, Ju C, et al.. Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities. Cell Mol Immunol, 2021, 18(1): 45-56

[38] Gomes LF, Lorente S, Simon-Giavarotti KA, et al.. Triiodothyronine differentially induces Kupffer cell ED1/ED2 subpopulations. Mol Aspects Med, 2004, 25(1–2): 183-190

[39] Lima FR, Gervais A, Colin C, et al.. Regulation of microglial development: a novel role for thyroid hormone. J Neurosci, 2001, 21(6): 2028-2038

[40] Nam SM, Kim YN, Yoo DY, et al.. Hypothyroidism affects astrocyte and microglial morphology in type 2 diabetes. Neural Regen Res, 2013, 8(26): 2458-2467

[41] Perrotta C, Buldorini M, Assi E, et al.. The thyroid hormone triiodothyronine controls macrophage maturation and functions: protective role during inflammation. Am J Pathol, 2014, 184(1): 230-247

[42] López-Mateo I, Rodríguez-Muñoz D, de La Rosa JV, et al.. Regulation of metabolic and transcriptional responses by the thyroid hormone in cellular models of murine macrophages. Front Immunol, 2022, 13: 923727

[43] Borse V, Kaur T, Hinton A, et al.. Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea. Front Cell Dev Biol, 2021, 9: 777836

[44] Mori Y, Tomonaga D, Kalashnikova A, et al.. Effects of 3,3′,5-triiodothyronine on microglial functions. Glia, 2015, 63(5): 906-920

[45] Ortega E, Forner MA, Garcia JJ, et al.. Enhanced chemotaxis of macrophages by strenuous exercise in trained mice: thyroid hormones as possible mediators. Mol Cell Biochem, 1999, 201(1–2): 41-47

[46] Forner MA, Barriga C, Ortega E. Exercise-induced stimulation of murine macrophage phagocytosis may be mediated by thyroxine. J Appl Physiol (1985), 1996, 80(3): 899-903

[47] Rosa LF, Safi DA, Curi R. Effect of hypo- and hyperthyroidism on the function and metabolism of macrophages in rats. Cell Biochem Funct, 1995, 13(2): 141-147

[48] Chen Y, Sjölinder M, Wang X, et al.. Thyroid hormone enhances nitric oxide-mediated bacterial clearance and promotes survival after meningococcal infection. PLoS One, 2012, 7(7): e41445

[49] Fernández V, Tapia G, Varela P, et al.. Redox regulation of thyroid hormone-induced Kupffer cell-dependent IkappaB-alpha phosphorylation in relation to inducible nitric oxide synthase expression. Free Radic Res, 2005, 39(4): 411-418

[50] Kwakkel J, Surovtseva OV, de Vries EM, et al.. A novel role for the thyroid hormone-activating enzyme type 2 deiodinase in the inflammatory response of macrophages. Endocrinology, 2014, 155(7): 2725-2734

[51] Gan S, Yang M, Fan L, et al.. Triiodothyronine Attenuates Silica-Induced Oxidative Stress, Inflammation, and Apoptosis via Thyroid Hormone Receptor a in Differentiated THP-1 Macrophages. Chem Res Toxicol, 2020, 33(5): 1256-1265

[52] Sun G, Hou X, Zhang L, et al.. 3,5,3′-Triiodothyronine-Loaded Liposomes Inhibit Hepatocarcinogenesis Via Inflammation-Associated Macrophages. Front Oncol, 2022, 12: 877982

[53] Rittenhouse PA, Redei E. Thyroxine administration prevents streptococcal cell wall-induced inflammatory responses. Endocrinology, 1997, 138(4): 1434-1439

[54] Billon C, Canaple L, Fleury S, et al.. TRa protects against atherosclerosis in male mice: identification of a novel anti-inflammatory property for TRα in mice. Endocrinology, 2014, 155(7): 2735-2745

[55] Chen Z, Cai D, Xie Y, et al.. Triiodothyronine induces a proinflammatory monocyte/macrophage profile and impedes cardiac regeneration. J Mol Cell Cardiol, 2024, 191: 7-11

[56] Yang M, Wang D, Gan S, et al.. Triiodothyronine ameliorates silica-induced pulmonary inflammation and fibrosis in mice. Sci Total Environ, 2021, 790: 148041

[57] Furuya F, Ishii T, Tamura S, et al.. The ligand-bound thyroid hormone receptor in macrophages ameliorates kidney injury via inhibition of nuclear factor-κB activities. Sci Rep, 2017, 7: 43960

[58] He W, Huang C, Wang L, et al.. The correlation between triiodothyronine and the severity of liver fibrosis. BMC Endocr Disord, 2022, 22(1): 313

[59] Tapia G, Santibáñez C, Farías J, et al.. Kupffer-cell activity is essential for thyroid hormone rat liver preconditioning. Mol Cell Endocrinol, 2010, 323(2): 292-297

[60] Islam SU, Lee JH, Shehzad A, et al.. Decursinol Angelate Inhibits LPS-Induced Macrophage Polarization through Modulation of the NFκB and MAPK Signaling Pathways. Molecules, 2018, 23(8): 1880

[61] Adam GO, Kim GB, Lee SJ, et al.. Red Ginseng Reduces Inflammatory Response via Suppression MAPK/P38 Signaling and p65 Nuclear Proteins Translocation in Rats and Raw 264.7 Macrophage. Am J Chin Med, 2019, 47(7): 1589-1609

[62] Wang S, Ni L, Fu X, et al.. A Sulfated Polysaccharide from Saccharina japonica Suppresses LPS-Induced Inflammation Both in a Macrophage Cell Model via Blocking MAPK/NF-κB Signal Pathways In Vitro and a Zebrafish Model of Embryos and Larvae In Vivo. Mar Drugs, 2020, 18(12): 593

[63] Contreras-Jurado C, Alonso-Merino E, Saiz-Ladera C, et al.. The Thyroid Hormone Receptors Inhibit Hepatic Interleukin-6 Signaling During Endotoxemia. Sci Rep, 2016, 6: 30990

[64] Yang Y, Jia Y, Ning Y, et al.. TAK1-AMPK Pathway in Macrophages Regulates Hypothyroid Atherosclerosis. Cardiovasc Drugs Ther, 2021, 35(3): 599-612

[65] Curi R, de Siqueira Mendes R, de Campos Crispin LA, et al.. A past and present overview of macrophage metabolism and functional outcomes. Clin Sci (Lond), 2017, 131(12): 1329-1342

[66] Rodriguez AE, Ducker GS, Billingham LK, et al.. Serine Metabolism Supports Macrophage IL-1β Production. Cell Metab, 2019, 29(4): 1003-1011

[67] Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology, 2013, 38(1): 23-38

[68] Shepherd R, Kim B, Saffery R, Novakovic B. Triiodothyronine (T3) Induces Limited Transcriptional and DNA Methylation Reprogramming in Human Monocytes. Biomedicines, 2022, 10(3): 608