Group 3 innate lymphoid cells require BATF to regulate gut homeostasis in mice. J Exp Med 2022 Nov 07;219(11)
Date
09/02/2022Pubmed ID
36048018Pubmed Central ID
PMC9440727DOI
10.1084/jem.20211861Scopus ID
2-s2.0-85137136864 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
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-γ production, dysbiosis, aberrant T cell immune responses, and spontaneous inflammatory bowel disease (IBD), which was considerably ameliorated by the removal of adaptive immunity, interferon-γ 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.
Author List
Wu X, Khatun A, Kasmani MY, Chen Y, Zheng S, Atkinson S, Nguyen C, Burns R, Taparowsky EJ, Salzman NH, Hand TW, Cui WAuthor
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBasic-Leucine Zipper Transcription Factors
Chromatin
Homeostasis
Immunity, Innate
Interferon-gamma
Intestinal Mucosa
Lymphocytes
Mice
