Circadian metabolism in myeloid cells

Yingxi Xu , Chen Wang , Ping-Chih Ho

Life Metabolism ›› 2025, Vol. 4 ›› Issue (4) : loaf018

PDF (352KB)
Life Metabolism ›› 2025, Vol. 4 ›› Issue (4) : loaf018 DOI: 10.1093/lifemeta/loaf018
Minireview

Circadian metabolism in myeloid cells

Author information +
History +
PDF (352KB)

Abstract

Circadian rhythms are fundamental regulators of physiological processes, including immune function. Recent insights uncover that not only lymphocytes but also myeloid cells possess intrinsic circadian clocks that govern their behavior and function. Emerging evidence highlights how circadian regulation of metabolism critically shapes the inflammatory and tissue-repair functions of myeloid subsets. Furthermore, mitochondrial dynamics, a key metabolic feature, are under circadian control and influence antigen presentation and effector functions. Here, we review the interplay between circadian clocks, metabolism, and myeloid immunity, discussing their therapeutic opportunities for optimizing vaccination, infection management, and immunotherapy.

Keywords

circadian rhythms / myeloid cell / metabolism

Cite this article

Download citation ▾
Yingxi Xu, Chen Wang, Ping-Chih Ho. Circadian metabolism in myeloid cells. Life Metabolism, 2025, 4(4): loaf018 DOI:10.1093/lifemeta/loaf018

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Scheiermann C , Gibbs J , Ince L et al. Clocking in to immunity. Nat Rev Immunol 2018; 18: 423- 37.

[2]

Hou Y , Wu Y , Cao Y et al. Optimizing stem cell infusion timing in the prevention of acute graft-versus-host disease. Cell 2025; 188: 3030- 44.e17.

[3]

Wang C , Zeng Q , Gul ZM et al. Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy. Cell 2024; 187: 2690- 702.e17.

[4]

Tahara Y , Shiraishi T , Kikuchi Y et al. Entrainment of the mouse circadian clock by sub-acute physical and psychological stress. Sci Rep 2015; 5: 11417.

[5]

Pitts S , Perone E , Silver R . Food-entrained circadian rhythms are sustained in arrhythmic Clk/Clk mutant mice. Am J Physiol Regul Integr Comp Physiol 2003; 285: R57- 67.

[6]

Scheiermann C , Kunisaki Y , Frenette PS . Circadian control of the immune system. Nat Rev Immunol 2013; 13: 190- 8.

[7]

Niu Y , Heddes M , Altaha B et al. Targeting the intestinal circadian clock by meal timing ameliorates gastrointestinal inflammation. Cell Mol Immunol 2024; 21: 842- 55.

[8]

Wang C , Lutes LK , Barnoud C et al. The circadian immune system. Sci Immunol 2022; 7: eabm2465.

[9]

Wager-Smith K , Kay SA . Circadian rhythm genetics: from flies to mice to humans. Nat Genet 2000; 26: 23- 7.

[10]

Takahashi JS . Transcriptional architecture of the mammalian circadian clock. Nat Rev Genet 2017; 18: 164- 79.

[11]

Halberg F , Johnson EA , Brown BW et al. Susceptibility rhythm to E. coli endotoxin and bioassay. Proc Soc Exp Biol Med 1960; 103: 142- 4.

[12]

He W , Holtkamp S , Hergenhan SM et al. Circadian expression of migratory factors establishes lineage-specific signatures that guide the homing of leukocyte subsets to tissues. Immunity 2018; 49: 1175- 90.e7.

[13]

Wyse C , O’Malley G , Coogan AN et al. Seasonal and daytime variation in multiple immune parameters in humans: evidence from 329,261 participants of the UK Biobank cohort. iScience 2021; 24: 102255.

[14]

Nguyen KD , Fentress SJ , Qiu Y et al. Circadian gene Bmal1 regulates diurnal oscillations of Ly6Chi inflammatory monocytes. Science 2013; 341: 1483- 8.

[15]

Cossio I , Lucas D , Hidalgo A . Neutrophils as regulators of the hematopoietic niche. Blood 2019; 133: 2140- 8.

[16]

Baxter M , Ray DW . Circadian rhythms in innate immunity and stress responses. Immunology 2020; 161: 261- 7.

[17]

Pick R , He W , Chen CS et al. Time-of-day-dependent trafficking and function of leukocyte subsets. Trends Immunol 2019; 40: 524- 37.

[18]

Wang S , Li F , Lin Y et al. Targeting REV-ERBα for therapeutic purposes: promises and challenges. Theranostics 2020; 10: 4168- 82.

[19]

Timmons GA , O’Siorain JR , Kennedy OD et al. Innate rhythms: clocks at the center of monocyte and macrophage function. Front Immunol 2020; 11: 1743.

[20]

Fortier EE , Rooney J , Dardente H et al. Circadian variation of the response of T cells to antigen. J Immunol 2011; 187: 6291- 300.

[21]

Bollinger T , Leutz A , Leliavski A et al. Circadian clocks in mouse and human CD4+ T cells. PLoS One 2011; 6: e29801.

[22]

Challet E . The circadian regulation of food intake. Nat Rev Endocrinol 2019; 15: 393- 405.

[23]

Keller M , Mazuch J , Abraham U et al. A circadian clock in macrophages controls inflammatory immune responses. Proc Natl Acad Sci USA 2009; 106: 21407- 12.

[24]

Xu H , Li H , Woo SL et al. Myeloid cell-specific disruption of Period1 and Period2 exacerbates diet-induced inflammation and insulin resistance. J Biol Chem 2014; 289: 16374- 88.

[25]

Oishi Y , Hayashi S , Isagawa T et al. Bmal1 regulates inflammatory responses in macrophages by modulating enhancer RNA transcription. Sci Rep 2017; 7: 7086.

[26]

Kitchen GB , Cunningham PS , Poolman TM et al. The clock gene Bmal1 inhibits macrophage motility, phagocytosis, and impairs defense against pneumonia. Proc Natl Acad Sci USA 2020; 117: 1543- 51.

[27]

Early JO , Menon D , Wyse CA et al. Circadian clock protein BMAL1 regulates IL-1β in macrophages via NRF2. Proc Natl Acad Sci USA 2018; 115: E8460- 8.

[28]

Pourcet B , Zecchin M , Ferri L et al. Nuclear receptor subfamily 1 group D member 1 regulates circadian activity of NLRP3 inflammasome to reduce the severity of fulminant hepatitis in mice. Gastroenterology 2018; 154: 1449- 64.e20.

[29]

Gibbs JE , Blaikley J , Beesley S et al. The nuclear receptor REV-ERBα mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines. Proc Natl Acad Sci USA 2012; 109: 582- 7.

[30]

Sato S , Sakurai T , Ogasawara J et al. A circadian clock gene, Reverba, modulates the inflammatory function of macrophages through the negative regulation of Ccl2 expression. J Immunol 2014; 192: 407- 17.

[31]

Griffin P , Dimitry JM , Sheehan PW et al. Circadian clock protein Rev-erbα regulates neuroinflammation. Proc Natl Acad Sci USA 2019; 116: 5102- 7.

[32]

Adrover JM , Del Fresno C , Crainiciuc G et al. A neutrophil timer coordinates immune defense and vascular protection. Immunity 2019; 50: 390- 402.e10.

[33]

Zhang D , Chen G , Manwani D et al. Neutrophil ageing is regulated by the microbiome. Nature 2015; 525: 528- 32.

[34]

Vicanolo T , Ozcan A , Li JL et al. Matrix-producing neutrophils populate and shield the skin. Nature 2025; 641: 740- 8.

[35]

Casanova-Acebes M , Pitaval C , Weiss LA et al. Rhythmic modulation of the hematopoietic niche through neutrophil clearance. Cell 2013; 153: 1025- 35.

[36]

Crespo M , Gonzalez-Teran B , Nikolic I et al. Neutrophil infiltration regulates clock-gene expression to organize daily hepatic metabolism. Elife 2020; 9: e59258.

[37]

Casanova-Acebes M , Nicolas-Avila JA , Li JL et al. Neutrophils instruct homeostatic and pathological states in naive tissues. J Exp Med 2018; 215: 2778- 95.

[38]

Holtkamp SJ , Ince LM , Barnoud C et al. Circadian clocks guide dendritic cells into skin lymphatics. Nat Immunol 2021; 22: 1375- 81.

[39]

Wang C , Barnoud C , Cenerenti M et al. Dendritic cells direct circadian anti-tumor immune responses. Nature 2023; 614: 136- 43.

[40]

Amir M , Campbell S , Kamenecka TM et al. Pharmacological modulation and genetic deletion of REV-ERBα and REV-ERBβ regulates dendritic cell development. Biochem Biophys Res Commun 2020; 527: 1000- 7.

[41]

Nobis CC , Dubeau Laramee G , Kervezee L et al. The circadian clock of CD8 T cells modulates their early response to vaccination and the rhythmicity of related signaling pathways. Proc Natl Acad Sci USA 2019; 116: 20077- 86.

[42]

Cervantes-Silva MP , Carroll RG , Wilk MM et al. The circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing. Nat Commun 2022; 13: 7217.

[43]

Ince LM , Barnoud C , Lutes LK et al. Influence of circadian clocks on adaptive immunity and vaccination responses. Nat Commun 2023; 14: 476.

[44]

Yipeng Z , Chao C , Ranran L et al. Metabolism: a potential regulator of neutrophil fate. Front Immunol 2024; 15: 1500676.

[45]

Vilbois S , Xu Y , Ho PC . Metabolic interplay: tumor macrophages and regulatory T cells. Trends Cancer 2024; 10: 242- 55.

[46]

Palsson-McDermott EM , Curtis AM , Goel G et al. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages. Cell Metab 2015; 21: 65- 80.

[47]

Cornice J , Verzella D , Arboretto P et al. NF-κB: governing macrophages in cancer. Genes (Basel) 2024; 15: 197.

[48]

Freemerman AJ , Johnson AR , Sacks GN et al. Metabolic reprogramming of macrophages: glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype. J Biol Chem 2014; 289: 7884- 96.

[49]

Huang SC , Everts B , Ivanova Y et al. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol 2014; 15: 846- 55.

[50]

Arlauckas SP , Garren SB , Garris CS et al. Arg1 expression defines immunosuppressive subsets of tumor-associated macrophages. Theranostics 2018; 8: 5842- 54.

[51]

Liu PS , Wang H , Li X et al. α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol 2017; 18: 985- 94.

[52]

Liu PS , Chen YT , Li X et al. CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage antitumorigenic functions. Nat Immunol 2023; 24: 452- 62.

[53]

Guan D , Lazar MA . Interconnections between circadian clocks and metabolism. J Clin Invest 2021; 131: e148278.

[54]

Sun Y , Jiang W , Horng T . Circadian metabolism regulates the macrophage inflammatory response. Life Metab. 2022; 1: 224- 33.

[55]

Collins EJ , Cervantes-Silva MP , Timmons GA et al. Post-transcriptional circadian regulation in macrophages organizes temporally distinct immunometabolic states. Genome Res 2021; 31: 171- 85.

[56]

Pan X , Jiang XC , Hussain MM . Impaired cholesterol metabolism and enhanced atherosclerosis in Clock mutant mice. Circulation 2013; 128: 1758- 69.

[57]

Wang Y , Pati P , Xu Y et al. Endotoxin disrupts circadian rhythms in macrophages via reactive oxygen species. PLoS One 2016; 11: e0155075.

[58]

Alexander RK , Liou YH , Knudsen NH et al. Bmal1 integrates mitochondrial metabolism and macrophage activation. Elife 2020; 9: e54090.

[59]

Timmons GA , Carroll RG , O’Siorain JR et al. The circadian clock protein BMAL1 acts as a metabolic sensor in macrophages to control the production of pro IL-1β.Front Immunol 2021; 12: 700431.

[60]

Reinke H , Asher G . Crosstalk between metabolism and circadian clocks. Nat Rev Mol Cell Biol 2019; 20: 227- 41.

[61]

Feigin RD , Klainer AS , Beisel WR . Circadian periodicity of blood amino-acids in adult men. Nature 1967; 215: 512- 4.

[62]

Giovanelli P , Sandoval TA , Cubillos-Ruiz JR . Dendritic cell metabolism and function in tumors. Trends Immunol 2019; 40: 699- 718.

[63]

Moller SH , Wang L , Ho PC . Metabolic programming in dendritic cells tailors immune responses and homeostasis. Cell Mol Immunol 2022; 19: 370- 83.

[64]

Hopwood TW , Hall S , Begley N et al. The circadian regulator BMAL1 programmes responses to parasitic worm infection via a dendritic cell clock. Sci Rep 2018; 8: 3782.

[65]

Zhou W , Hsu AY , Wang Y et al. Mitofusin 2 regulates neutrophil adhesive migration and the actin cytoskeleton. J Cell Sci 2020; 133: jcs248880.

[66]

Amini P , Stojkov D , Felser A et al. Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production. Nat Commun 2018; 9: 2958.

RIGHTS & PERMISSIONS

The Author(s). Published by Oxford University Press on behalf of Higher Education Press.

AI Summary AI Mindmap
PDF (352KB)

445

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/