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:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84882640205&partnerID=40&md5=c52bdb309cea4b43b23c41881496234f
Notes:	--- - "Export Date: 1 October 2013" - "CODEN: IUNIE" - "Source: Scopus"

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