Transforming growth factor-β signaling curbs thymic negative selection promoting regulatory T cell development Journal Article
| Authors: | Ouyang, W.; Beckett, O.; Ma, Q.; Li, M. O. |
| Article Title: | Transforming growth factor-β signaling curbs thymic negative selection promoting regulatory T cell development |
| Abstract: | Thymus-derived naturally occurring regulatory T (nTreg) cells are necessary for immunological self-tolerance. nTreg cell development is instructed by the T cell receptor and can be induced by agonist antigens that trigger T cell-negative selection. How T cell deletion is regulated so that nTreg cells are generated is unclear. Here we showed that transforming growth factor-β (TGF-β) signaling protected nTreg cells and antigen-stimulated conventional T cells from apoptosis. Enhanced apoptosis of TGF-β receptor-deficient nTreg cells was associated with high expression of proapoptotic proteins Bim, Bax, and Bak and low expression of the antiapoptotic protein Bcl-2. Ablation of Bim in mice corrected the Treg cell development and homeostasis defects. Our results suggest that nTreg cell commitment is independent of TGF-β signaling. Instead, TGF-β promotes nTreg cell survival by antagonizing T cell negative selection. These findings reveal a critical function for TGF-β in control of autoreactive T cell fates with important implications for understanding T cell self-tolerance mechanisms. © 2010 Elsevier Inc. |
| Keywords: | signal transduction; controlled study; protein expression; proto-oncogene proteins; nonhuman; flow cytometry; polymerase chain reaction; protein function; animal cell; mouse; animals; mice; mice, knockout; animal tissue; cells, cultured; protein bcl 2; apoptosis; models, biological; cell maturation; transforming growth factor beta; bim protein; apoptosis regulatory proteins; membrane proteins; regulatory t lymphocyte; lymphocyte activation; t-lymphocytes, regulatory; thymus gland; protein-serine-threonine kinases; immunoblotting; receptors, transforming growth factor beta; homeostasis; molimmuno; cell protection; cell metabolism; thymocyte; t lymphocyte activation; cell selection; cellimmuno; transforming growth factor beta receptor 2; protein bax; protein bak |
| Journal Title: | Immunity |
| Volume: | 32 |
| Issue: | 5 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2010-05-28 |
| Start Page: | 642 |
| End Page: | 653 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2010.04.012 |
| PUBMED: | 20471291 |
| PROVIDER: | scopus |
| PMCID: | PMC2880228 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 20 April 2011" - "CODEN: IUNIE" - "Source: Scopus" |
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