Shizue Tani-ichi, Akihiro Shimba, Keisuke Wagatsuma, Hitoshi Miyachi, Satsuki Kitano, Kumiko Imai, Takahiro Hara, Koichi Ikuta
Proceedings of the National Academy of Sciences of the United States of America 2013 Jan 08Interleukin (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.
Shizue Tani-ichi, Akihiro Shimba, Keisuke Wagatsuma, Hitoshi Miyachi, Satsuki Kitano, Kumiko Imai, Takahiro Hara, Koichi Ikuta. Interleukin-7 receptor controls development and maturation of late stages of thymocyte subpopulations. Proceedings of the National Academy of Sciences of the United States of America. 2013 Jan 08;110(2):612-7
PMID: 23267098
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