Foxp3-independent mechanism by which TGF-β controls peripheral T cell tolerance
Foxp3-independent mechanism by which TGF-β controls peripheral T cell tolerance
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DOI：
10.1073/pnas.1706356114
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发表时间：
2017-09-05
影响因子：
11.1
通讯作者：
Li, Ming O.
中科院分区：
文献类型：
--
作者：
Oh, Soyoung A.;Liu, Ming;Li, Ming O.
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 (T beta RII) 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.
