Regulatory T Cell TGF-B1 Regulates Distinct Checkpoints Governing Allergy and Autoimmunity

immunology;T cell;regulatory T cell;tolerance;tgfb1;transforming growth factor beta;food allergy;autoimmunity;dysbiosis;commensal microbiota

Turner, Jacob ; Oettgen, Hans,Anderson, Ana,Boussiotis, Vicki,Huseby, Eric

University:Havard University

Department:Medical Sciences

关键词: immunology;    T cell;    regulatory T cell;    tolerance;    tgfb1;    transforming growth factor beta;    food allergy;    autoimmunity;    dysbiosis;    commensal microbiota;   

Others  :  https://dash.harvard.edu/bitstream/handle/1/37365927/TURNER-DISSERTATION-2020.pdf?sequence=1&isAllowed=y

美国|英语

来源: Digital Access to Scholarship at Harvard

【 摘 要 】

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) have decreased expression of transforming growth factor beta 1 (TGF- b1) due to IL-4 and STAT6-dependent inhibition of Tgfb1 transcription. These changes were modelled by Treg cell-specific Tgfb1 monoallelic inactivation, which induced allergic dysregulation by impairing microbiota dependent ROR-gt+ 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 for Treg cell-derived TGF- b1 in regulating allergy and autoimmunity at distinct checkpoints in a Tgfb1 gene dose and microbiota-dependent manner.