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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2013-01, Vol.110 (2), p.612-617
• Main Authors: Tani-ichi, Shizue, Shimba, Akihiro, Wagatsuma, Keisuke, Miyachi, Hitoshi, Kitano, Satsuki, Imai, Kumiko, Hara, Takahiro, Ikuta, Koichi
• Format: Article
• Language: English
• Subjects: Animals; B lymphocytes; Biological Sciences; Bromodeoxyuridine; Cell Differentiation - immunology; Core Binding Factor alpha Subunits - metabolism; Cytokines; Developmental biology; Flow Cytometry; Gene expression; Government regulation; Homeostasis; Interleukin-7 Receptor alpha Subunit - genetics; Interleukin-7 Receptor alpha Subunit - metabolism; Lymphocyte Subsets - metabolism; Lymphocyte Subsets - physiology; Mice; Mice, Knockout; Natural killer T cells; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Real-Time Polymerase Chain Reaction; Receptors; Reverse Transcriptase Polymerase Chain Reaction; Rodents; T cell antigen receptors; T cell receptors; T lymphocytes; Thymocytes; Thymocytes - cytology; Thymocytes - metabolism; Transgenes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1219242110

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.