TGF-β cytokine signaling promotes CD8+ T cell development and low-affinity CD4+ T cell homeostasis by regulation of interleukin-7 receptor α expression Journal Article
| Authors: | Ouyang, W.; Oh, S.; Ma, Q.; Bivona, M.; Zhu, J.; Li, M. |
| Article Title: | TGF-β cytokine signaling promotes CD8+ T cell development and low-affinity CD4+ T cell homeostasis by regulation of interleukin-7 receptor α expression |
| Abstract: | Interleukin-7 receptor α chain (IL-7Rα) is induced upon Tcell positive selection and controls thymic CD8-lineage specification and peripheral naive Tcell homeostasis. How IL-7Rα expression is regulated in developing thymocytes is unclear. Here, we show that transforming growth factor β (TGF-β) signaling promoted IL-7Rα expression and CD8+ Tcell differentiation. In addition, TGF-β signaling was required for high IL-7Rα expression in CD4+ Tcells bearing low-affinity Tcell receptors, and the abrogation of TGF-β receptor expression led to failed maintenance of peripheral CD4+ Tcells. Compromised IL-7Rα expression in TGF-β-receptor-deficientTcells was associated with increased expression of the Il7ra transcriptional repressor, Gfi-1. IL-7Rα transgenesis or T-cell-specific ablation of Gfi-1 restored IL-7Rα expression and largely ameliorated the development and homeostasis defects of TGF-β-receptor-deficient Tcells. These findings reveal functions for TGF-β signaling in controlling IL-7Rα expression and in promoting Tcell repertoire diversification. © 2013 Elsevier Inc. |
| Keywords: | signal transduction; protein expression; dna-binding proteins; nonhuman; cd8+ t lymphocyte; cd8-positive t-lymphocytes; mouse; animals; mice; mice, knockout; transforming growth factor beta; animal experiment; cell differentiation; cell lineage; transgenic mouse; transcription factors; immune response; receptors, antigen, t-cell; protein-serine-threonine kinases; cd4+ t lymphocyte; cd4-positive t-lymphocytes; receptors, transforming growth factor beta; homeostasis; interleukin 7 receptor alpha; receptors, interleukin-7; transgenics; homeostasis and regulation |
| Journal Title: | Immunity |
| Volume: | 39 |
| Issue: | 2 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2013-08-22 |
| Start Page: | 335 |
| End Page: | 346 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2013.07.016 |
| PROVIDER: | scopus |
| PUBMED: | 23932572 |
| PMCID: | PMC3801187 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 October 2013" - "CODEN: IUNIE" - "Source: Scopus" |
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