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Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):612-7. doi: 10.1073/pnas.1219242110. Epub 2012 Dec 24.

Interleukin-7 receptor controls development and maturation of late stages of thymocyte subpopulations.

Author information

1
Laboratory of Biological Protection, Department of Biological Responses and Reproductive Engineering Team, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan. staniich@virus.kyoto-u.ac.jp

Abstract

Interleukin (IL)-7 is a cytokine essential for T lymphocyte development and homeostasis. However, little is known about the roles of IL-7 receptor α-chain (IL-7Rα) in late stages of T-cell development. To address this question, we established IL-7Rα-floxed mice and crossed them with CD4-Cre transgenic mice. Resultant IL-7R conditional knockout (IL-7RcKO) mice exhibited marked reduction in CD8 single positive (SP) T cells, regulatory T cells (Tregs), and natural killer T (NKT) cells in thymus. The proportion and proliferation of both mature CD4SP and CD8SP thymocytes were decreased without affecting Runx expression. In addition, expression of the glucocorticoid-induced TNF receptor was reduced in CD4SP and CD8SP thymocytes, and expression of CD5 was decreased in CD8SP thymocytes. IL-7RcKO mice also showed impaired Treg and NKT cell proliferation and inhibition of NKT cell maturation. Bcl-2 expression was reduced in CD4SP and CD8SP thymocytes but not in Tregs and NKT cells, and introduction of a Bcl-2 transgene rescued frequency and CD5 expression of CD8SP thymocytes. Furthermore, IL-7RcKO mice exhibited greatly increased numbers of B cells and, to a lesser extent, γδ T and dendritic cells in thymus. Overall, this study demonstrates that IL-7Rα differentially controls development and maturation of thymocyte subpopulations in late developmental stages and suggests that IL-7R expression on αβ T cells suppresses development of other cell lineages in thymus.

PMID:
23267098
PMCID:
PMC3545802
DOI:
10.1073/pnas.1219242110
[Indexed for MEDLINE]
Free PMC Article

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