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Bcl‐3 suppresses differentiation of RORγt + regulatory T cells
Author(s) -
Tang Wanhu,
Saret Sun,
Tian Ruxiao,
Wang Hongshan,
Claudio Estefania,
Murphy Philip M,
Siebenlist Ulrich
Publication year - 2021
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12441
Subject(s) - rar related orphan receptor gamma , gata3 , transcription factor , biology , immune system , phenotype , microbiology and biotechnology , cellular differentiation , immunotherapy , immunology , cancer research , chemistry , foxp3 , gene , genetics
Regulatory T cells (Tregs) exert inhibitory function under various physiological conditions and adopt diverse characteristics following environmental cues. Multiple subsets of Tregs expressing master transcription factors of helper T cells such as RORγt, T‐bet, Gata3 and PPARγ have been characterized, but the molecular mechanism governing the differentiation of these subsets remains largely unknown. Here we report that the atypical IκB protein family member Bcl‐3 suppresses RORγt + Treg accumulation. The suppressive effect of Bcl‐3 was particularly evident in the mouse immune tolerance model of anti‐CD3 therapy. Using conditional knockout mice, we illustrate that loss of Bcl‐3 specifically in Tregs was sufficient to boost RORγt + Treg formation and resistance of mice to dextran sulfate sodium‐induced colitis. We further demonstrate the suppressive effect of Bcl‐3 on RORγt + Treg differentiation in vitro . Our results reveal a novel role of nuclear factor‐kappa B signaling pathways in Treg subset differentiation that may have clinical implications in immunotherapy.