Group 3 innate lymphoid cells require BATF to regulate gut homeostasis in mice
JOURNAL OF EXPERIMENTAL MEDICINE(2022)
Abstract
ILC3s are crucial for the maintenance of host-microbiota homeostasis in gastrointestinal mucosal tissues. This study shows that BATF globally shapes the chromatin landscape of intestinal ILC3s, which in turn orchestrates microbiota and mucosal CD4(+) T cell immunity. Group 3 innate lymphoid cells (ILC3s) are crucial for the maintenance of host-microbiota homeostasis in gastrointestinal mucosal tissues. The mechanisms that maintain lineage identity of intestinal ILC3s and ILC3-mediated orchestration of microbiota and mucosal T cell immunity are elusive. Here, we identified BATF as a gatekeeper of ILC3 homeostasis in the gut. Depletion of BATF in ILC3s resulted in excessive interferon-gamma production, dysbiosis, aberrant T cell immune responses, and spontaneous inflammatory bowel disease (IBD), which was considerably ameliorated by the removal of adaptive immunity, interferon-gamma blockade, or antibiotic treatment. Mechanistically, BATF directly binds to the cis-regulatory elements of type 1 effector genes, restrains their chromatin accessibility, and inhibits their expression. Conversely, BATF promotes chromatin accessibility of genes involved in MHCII antigen processing and presentation pathways, which in turn directly promotes the transition of precursor ILC3s to MHCII+ ILC3s. Collectively, our findings reveal that BATF is a key transcription factor for maintaining ILC3 stability and coordinating ILC3-mediated control of intestinal homeostasis.
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Key words
gut homeostasis,lymphoid cells,batf,mice
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