Foxp3-independent mechanism by which TGF-β controls peripheral T cell tolerance Journal Article
| Authors: | Oh, S. A.; Liu, M.; Nixon, B. G.; Kang, D.; Toure, A.; Bivona, M.; Li, M. O. |
| Article Title: | Foxp3-independent mechanism by which TGF-β controls peripheral T cell tolerance |
| Abstract: | Peripheral T cell tolerance is promoted by the regulatory cytokine TGF-β and Foxp3-expressing Treg cells. However, whether TGF-β 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-β receptor II (TβRII) 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-β 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. © 2017, National Academy of Sciences. All rights reserved. |
| Keywords: | autoimmunity; tolerance; t cell; tgf-β |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 114 |
| Issue: | 36 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2017-09-05 |
| Start Page: | E7536 |
| End Page: | E7544 |
| Language: | English |
| DOI: | 10.1073/pnas.1706356114 |
| PROVIDER: | scopus |
| PMCID: | PMC5594672 |
| PUBMED: | 28827353 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 October 2017 -- Source: Scopus |
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