title: Interleukin-7 receptor controls development and maturation of late stages of thymocyte subpopulations.
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.
authors.affiliation: 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
authors.forename: Shizue
authors.initials: S
authors.lastname: Tani-ichi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shimba
authors.forename: Keisuke
authors.initials: K
authors.lastname: Wagatsuma
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyachi
authors.forename: Satsuki
authors.initials: S
authors.lastname: Kitano
authors.forename: Kumiko
authors.initials: K
authors.lastname: Imai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hara
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000276:immunology*; D050657:Core Binding Factor alpha Subunits / Q000378:metabolism; D005434:Flow Cytometry; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060168:Thymocytes / Q000166:cytology* / Q000378:metabolism
chemical_list: D050657:Core Binding Factor alpha Subunits; D053699:Interleukin-7 Receptor alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D001973:Bromodeoxyuridine