| First Author | Turner JA | Year | 2020 |
| Journal | Immunity | Volume | 53 |
| Issue | 6 | Pages | 1202-1214.e6 |
| PubMed ID | 33086036 | Mgi Jnum | J:305828 |
| Mgi Id | MGI:6706568 | Doi | 10.1016/j.immuni.2020.10.002 |
| Citation | Turner JA, et al. (2020) Regulatory T Cell-Derived TGF-beta1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity. Immunity 53(6):1202-1214.e6 |
| abstractText | 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-beta1) 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-gammat)(+) 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-beta1 in regulating allergy and autoimmunity at distinct checkpoints in a Tgfb1 gene dose- and microbiota-dependent manner. |
