A circadian clock is essential for homeostasis of group 3 innate lymphoid cells in the gut.

TitleA circadian clock is essential for homeostasis of group 3 innate lymphoid cells in the gut.
Publication TypeJournal Article
Year of Publication2019
AuthorsTeng, F, Goc, J, Zhou, L, Chu, C, Shah, MA, Eberl, G, Sonnenberg, GF
JournalSci Immunol
Volume4
Issue40
Date Published2019 Oct 04
ISSN2470-9468
Abstract

Group 3 innate lymphoid cells (ILC3s) critically orchestrate host-microbe interactions in the healthy mammalian intestine and become substantially impaired in the context of inflammatory bowel disease (IBD). However, the molecular pathways controlling the homeostasis of ILC3s remain incompletely defined. Here, we identify that intestinal ILC3s are highly enriched in expression of genes involved in the circadian clock and exhibit diurnal oscillations of these pathways in response to light cues. Classical ILC3 effector functions also exhibited diurnal oscillations, and lineage-specific deletion of BMAL1, a master regulator of the circadian clock, resulted in markedly reduced ILC3s selectively in the intestine. BMAL1-deficient ILC3s exhibit impaired expression of and , hyperactivation of RORĪ³t-dependent target genes, and elevated proapoptotic pathways. Depletion of the microbiota with antibiotics partially reduced the hyperactivation of BMAL1-deficient ILC3s and restored cellular homeostasis in the intestine. Last, ILC3s isolated from the inflamed intestine of patients with IBD exhibit substantial alterations in expression of several circadian-related genes. Our results collectively define that circadian regulation is essential for the homeostasis of ILC3s in the presence of a complex intestinal microbiota and that this pathway is disrupted in the context of IBD.

DOI10.1126/sciimmunol.aax1215
Alternate JournalSci Immunol
PubMed ID31586011