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

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ID: 57738
2019
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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 RORγt-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.
Reference Key
teng2019ascience Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Teng, Fei;Goc, Jeremy;Zhou, Lei;Chu, Coco;Shah, Manish A;Eberl, Gérard;Sonnenberg, Gregory F;
Journal science immunology
Year 2019
DOI
eaax1215
URL
Keywords
melanoma macrophage gene expression transcription factor erna enhancer pu.1 chromatin modification interleukin 1 (il-1)

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