| Literature DB >> 33086036 |
Jacob A Turner1, Emmanuel Stephen-Victor1, Sen Wang1, Magali Noval Rivas2, Azza Abdel-Gadir1, Hani Harb1, Ye Cui1, Manoussa Fanny1, Louis-Marie Charbonnier1, Jason Jun Hung Fong1, Mehdi Benamar1, Leighanne Wang1, Oliver T Burton3, Kushagra Bansal4, Lynn Bry5, Chengsong Zhu6, Quan-Zhen Li6, Rachel L Clement7, Hans C Oettgen1, Elena Crestani1, Rima Rachid1, Peter T Sage7, Talal A Chatila8.
Abstract
The mechanisms by which regulatory T (Treg) cells differentially control allergic and autoimmune responses remain unclear. We show that Treg cells in food allergy (FA) had decreased expression of transforming growth factor beta 1 (TGF-β1) because of interleukin-4 (IL-4)- and signal transducer and activator of transciription-6 (STAT6)-dependent inhibition of Tgfb1 transcription. These changes were modeled by Treg cell-specific Tgfb1 monoallelic inactivation, which induced allergic dysregulation by impairing microbiota-dependent retinoic acid receptor-related orphan receptor gamma t (ROR-γt)+ Treg cell differentiation. This dysregulation was rescued by treatment with Clostridiales species, which upregulated Tgfb1 expression in Treg cells. Biallelic deficiency precipitated fatal autoimmunity with intense autoantibody production and dysregulated T follicular helper and B cell responses. These results identify a privileged role of Treg cell-derived TGF-β1 in regulating allergy and autoimmunity at distinct checkpoints in a Tgfb1 gene dose- and microbiota-dependent manner.Entities:
Keywords: ROR-γt; T follicular helper cells; TGF-β; allergy; autoimmunity; checkpoint; food allergy; mast cells; microbiota; regulatory T cells
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Year: 2020 PMID： 33086036 PMCID： PMC7744401 DOI： 10.1016/j.immuni.2020.10.002
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745