Circadian regulation of innate lymphoid cells

The interplay between intestinal microbes and immune cells ensures vital functions of the organism. However, inadequate host-microbe relationships lead to inflammatory diseases that are major public health concerns. As an example, inflammatory bowel disease is the result of inadequate immune responses and altered intestinal physiology.

Innate lymphoid cells ILC are an emergent family of effectors abundantly present at mucosal sites. Group 3 ILC ILC3 produce pro-inflammatory cytokines and regulate mucosal homeostasis, anti-microbial defence and adaptive immune responses. ILC3 development and function have been widely perceived to be programmed. However, recent evidence indicates that ILC3 are also controlled by dietary signals and neurotrophic factors. Nevertheless, how ILC3 perceive, integrate and respond to environmental cues remains mostly unexplored.

In this proposal, we hypothesize that circadian signals regulate intestinal ILC3 to prevent inflammation in anticipation to enteric challenges. Thus, we propose to employ genetic, cellular and molecular approaches to decipher how circadian environmental cues drive ILC3 homeostasis, function and intestinal defence.

Our ground-breaking research will establish a novel sensing program by which ILC3 integrate circadian environmental cues, shedding light into the intricate relationships between enteric immune cells, their genes, and their oscillatory environment in the healthy and inflamed intestine. Finally, our work will reveal new pathways that may be targeted in inflammatory diseases that are major Public Health concerns.