Immunity Around the Clock

Overview

Journal Science

Specialty Science

Date 2016 Nov 26

PMID 27885005

Citations 131

Authors

Kevin Man

Andrew Loudon

Ajay Chawla

Affiliations

Soon will be listed here.

Abstract

Immunity is a high-cost, high-benefit trait that defends against pathogens and noxious stimuli but whose overactivation can result in immunopathologies and sometimes even death. Because many immune parameters oscillate rhythmically with the time of day, the circadian clock has emerged as an important gatekeeper for reducing immunity-associated costs, which, in turn, enhances organismal fitness. This is mediated by interactions between extrinsic environmental cues and the intrinsic oscillators of immune cells, which together optimize immune responses throughout the circadian cycle. The elucidation of these clock-controlled immunomodulatory mechanisms might uncover new approaches for treating infections and chronic inflammatory diseases.

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References

Seillet C, Rankin L, Groom J, Mielke L, Tellier J, Chopin M . Nfil3 is required for the development of all innate lymphoid cell subsets. J Exp Med. 2014; 211(9):1733-40. PMC: 4144736. DOI: 10.1084/jem.20140145. View

Bass J, Takahashi J . Circadian integration of metabolism and energetics. Science. 2010; 330(6009):1349-54. PMC: 3756146. DOI: 10.1126/science.1195027. View

Hayashi M, Shimba S, Tezuka M . Characterization of the molecular clock in mouse peritoneal macrophages. Biol Pharm Bull. 2007; 30(4):621-6. DOI: 10.1248/bpb.30.621. View

Casanova-Acebes M, Pitaval C, Weiss L, Nombela-Arrieta C, Chevre R, A-Gonzalez N . Rhythmic modulation of the hematopoietic niche through neutrophil clearance. Cell. 2013; 153(5):1025-35. PMC: 4128329. DOI: 10.1016/j.cell.2013.04.040. View

Geiger T, Abt M, Gasteiger G, Firth M, OConnor M, Geary C . Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens. J Exp Med. 2014; 211(9):1723-31. PMC: 4144732. DOI: 10.1084/jem.20140212. View

Lam M, Cho H, Lesch H, Gosselin D, Heinz S, Tanaka-Oishi Y . Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription. Nature. 2013; 498(7455):511-5. PMC: 3839578. DOI: 10.1038/nature12209. View

Silver A, Arjona A, Walker W, Fikrig E . The circadian clock controls toll-like receptor 9-mediated innate and adaptive immunity. Immunity. 2012; 36(2):251-61. PMC: 3315694. DOI: 10.1016/j.immuni.2011.12.017. View

Scheiermann C, Kunisaki Y, Frenette P . Circadian control of the immune system. Nat Rev Immunol. 2013; 13(3):190-8. PMC: 4090048. DOI: 10.1038/nri3386. View

Zhang Y, Fang B, Emmett M, Damle M, Sun Z, Feng D . GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock. Science. 2015; 348(6242):1488-92. PMC: 4613749. DOI: 10.1126/science.aab3021. View

10.

Yu X, Rollins D, Ruhn K, Stubblefield J, Green C, Kashiwada M . TH17 cell differentiation is regulated by the circadian clock. Science. 2013; 342(6159):727-30. PMC: 4165400. DOI: 10.1126/science.1243884. View

11.

Gibbs J, Ince L, Matthews L, Mei J, Bell T, Yang N . An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action. Nat Med. 2014; 20(8):919-26. PMC: 4268501. DOI: 10.1038/nm.3599. View

12.

Bell-Pedersen D, Cassone V, Earnest D, Golden S, Hardin P, Thomas T . Circadian rhythms from multiple oscillators: lessons from diverse organisms. Nat Rev Genet. 2005; 6(7):544-56. PMC: 2735866. DOI: 10.1038/nrg1633. View

13.

Labrecque N, Cermakian N . Circadian Clocks in the Immune System. J Biol Rhythms. 2015; 30(4):277-90. DOI: 10.1177/0748730415577723. View

14.

Medzhitov R . Origin and physiological roles of inflammation. Nature. 2008; 454(7203):428-35. DOI: 10.1038/nature07201. View

15.

Curtis A, Bellet M, Sassone-Corsi P, ONeill L . Circadian clock proteins and immunity. Immunity. 2014; 40(2):178-86. DOI: 10.1016/j.immuni.2014.02.002. View

16.

Gibbs J, Blaikley J, Beesley S, Matthews L, Simpson K, Boyce S . The nuclear receptor REV-ERBα mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines. Proc Natl Acad Sci U S A. 2011; 109(2):582-7. PMC: 3258648. DOI: 10.1073/pnas.1106750109. View

17.

Scheiermann C, Kunisaki Y, Lucas D, Chow A, Jang J, Zhang D . Adrenergic nerves govern circadian leukocyte recruitment to tissues. Immunity. 2012; 37(2):290-301. PMC: 3428436. DOI: 10.1016/j.immuni.2012.05.021. View

18.

Fang B, Lazar M . Dissecting the Rev-erbα Cistrome and the Mechanisms Controlling Circadian Transcription in Liver. Cold Spring Harb Symp Quant Biol. 2015; 80:233-8. DOI: 10.1101/sqb.2015.80.027508. View

19.

Shackelford P, Feigin R . Periodicity of susceptibility to pneumococcal infection: influence of light and adrenocortical secretions. Science. 1973; 182(4109):285-7. DOI: 10.1126/science.182.4109.285. View

20.

Kawate T, Abo T, Hinuma S, Kumagai K . Studies of the bioperiodicity of the immune response. II. Co-variations of murine T and B cells and a role of corticosteroid. J Immunol. 1981; 126(4):1364-7. View