A conserved Bacteroidetes antigen induces anti-inflammatory intestinal T lymphocytes.

Publication Type Academic Article
Authors Bousbaine D, Fisch L, London M, Bhagchandani P, Rezende de Castro T, Mimee M, Olesen S, Reis B, VanInsberghe D, Bortolatto J, Poyet M, Cheloha R, Sidney J, Ling J, Gupta A, Lu T, Sette A, Alm E, Moon J, Victora G, Mucida D, Ploegh H, Bilate A
Journal Science
Volume 377
Issue 6606
Pagination 660-666
Date Published 08/04/2022
ISSN 1095-9203
Keywords Bacteroidetes, CD4-Positive T-Lymphocytes, Colitis, Intestinal Mucosa, beta-N-Acetylhexosaminidases
Abstract The microbiome contributes to the development and maturation of the immune system. In response to commensal bacteria, intestinal CD4+ T lymphocytes differentiate into functional subtypes with regulatory or effector functions. The development of small intestine intraepithelial lymphocytes that coexpress CD4 and CD8αα homodimers (CD4IELs) depends on the microbiota. However, the identity of the microbial antigens recognized by CD4+ T cells that can differentiate into CD4IELs remains unknown. We identified β-hexosaminidase, a conserved enzyme across commensals of the Bacteroidetes phylum, as a driver of CD4IEL differentiation. In a mouse model of colitis, β-hexosaminidase-specific lymphocytes protected against intestinal inflammation. Thus, T cells of a single specificity can recognize a variety of abundant commensals and elicit a regulatory immune response at the intestinal mucosa.
DOI 10.1126/science.abg5645
PubMed ID 35926021
PubMed Central ID PMC9766740
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