First Author | Tani-ichi S | Year | 2013 |
Journal | Proc Natl Acad Sci U S A | Volume | 110 |
Issue | 2 | Pages | 612-7 |
PubMed ID | 23267098 | Mgi Jnum | J:193283 |
Mgi Id | MGI:5468073 | Doi | 10.1073/pnas.1219242110 |
Citation | Tani-ichi S, et al. (2013) Interleukin-7 receptor controls development and maturation of late stages of thymocyte subpopulations. Proc Natl Acad Sci U S A 110(2):612-7 |
abstractText | Interleukin (IL)-7 is a cytokine essential for T lymphocyte development and homeostasis. However, little is known about the roles of IL-7 receptor alpha-chain (IL-7Ralpha) in late stages of T-cell development. To address this question, we established IL-7Ralpha-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, gammadelta T and dendritic cells in thymus. Overall, this study demonstrates that IL-7Ralpha differentially controls development and maturation of thymocyte subpopulations in late developmental stages and suggests that IL-7R expression on alphabeta T cells suppresses development of other cell lineages in thymus. |