In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 2 ( 2023-2-14), p. e3002000-
Abstract:
Multiple sclerosis (MS) is a T cell-driven autoimmune disease that attacks the myelin of the central nervous system (CNS) and currently has no cure. MS etiology is linked to both the gut flora and external environmental factors but this connection is not well understood. One immune system regulator responsive to nonpathogenic external stimuli is the aryl hydrocarbon receptor (AHR). The AHR, which binds diverse molecules present in the environment in barrier tissues, is a therapeutic target for MS. However, AHR’s precise function in T lymphocytes, the orchestrators of MS, has not been described. Here, we show that in a mouse model of MS, T cell-specific Ahr knockout leads to recovery driven by a decrease in T cell fitness. At the mechanistic level, we demonstrate that the absence of AHR changes the gut microenvironment composition to generate metabolites that impact T cell viability, such as bile salts and short chain fatty acids. Our study demonstrates a newly emerging role for AHR in mediating the interdependence between T lymphocytes and the microbiota, while simultaneously identifying new potential molecular targets for the treatment of MS and other autoimmune diseases.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002000
DOI:
10.1371/journal.pbio.3002000.g001
DOI:
10.1371/journal.pbio.3002000.g002
DOI:
10.1371/journal.pbio.3002000.g003
DOI:
10.1371/journal.pbio.3002000.g004
DOI:
10.1371/journal.pbio.3002000.g005
DOI:
10.1371/journal.pbio.3002000.g006
DOI:
10.1371/journal.pbio.3002000.s001
DOI:
10.1371/journal.pbio.3002000.s002
DOI:
10.1371/journal.pbio.3002000.s003
DOI:
10.1371/journal.pbio.3002000.s004
DOI:
10.1371/journal.pbio.3002000.s005
DOI:
10.1371/journal.pbio.3002000.s006
DOI:
10.1371/journal.pbio.3002000.s007
DOI:
10.1371/journal.pbio.3002000.s008
DOI:
10.1371/journal.pbio.3002000.s009
DOI:
10.1371/journal.pbio.3002000.r001
DOI:
10.1371/journal.pbio.3002000.r002
DOI:
10.1371/journal.pbio.3002000.r003
DOI:
10.1371/journal.pbio.3002000.r004
DOI:
10.1371/journal.pbio.3002000.r005
DOI:
10.1371/journal.pbio.3002000.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X
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