| First Author | Oh SA | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 36 | Pages | E7536-E7544 |
| PubMed ID | 28827353 | Mgi Jnum | J:273654 |
| Mgi Id | MGI:5921522 | Doi | 10.1073/pnas.1706356114 |
| Citation | Oh SA, et al. (2017) Foxp3-independent mechanism by which TGF-beta controls peripheral T cell tolerance. Proc Natl Acad Sci U S A 114(36):E7536-E7544 |
| abstractText | Peripheral T cell tolerance is promoted by the regulatory cytokine TGF-beta and Foxp3-expressing Treg cells. However, whether TGF-beta and Treg cells are part of the same regulatory module, or exist largely as distinct pathways to repress self-reactive T cells remains incompletely understood. Using a transgenic model of autoimmune diabetes, here we show that ablation of TGF-beta receptor II (TbetaRII) in T cells, but not Foxp3 deficiency, resulted in early-onset diabetes with complete penetrance. The rampant autoimmune disease was associated with enhanced T cell priming and elevated T cell expression of the inflammatory cytokine GM-CSF, concomitant with pancreatic infiltration of inflammatory monocytes that triggered immunopathology. Ablation of the GM-CSF receptor alleviated the monocyte response and inhibited disease development. These findings reveal that TGF-beta promotes T cell tolerance primarily via Foxp3-independent mechanisms and prevents autoimmunity in this model by repressing the cross talk between adaptive and innate immune systems. |
