期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 2, 页码 612-617出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1219242110
关键词
differentiation; survival
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [22790460, 24790469]
- Fujiwara Memorial Foundation
- BioLegend/Tomy Digital Biology Young Scientist Research Award
- Grants-in-Aid for Scientific Research [24790469, 22790460, 24790468, 23659202] Funding Source: KAKEN
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-7R alpha) in late stages of T-cell development. To address this question, we established IL-7R alpha-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, gamma delta T and dendritic cells in thymus. Overall, this study demonstrates that IL-7R alpha differentially controls development and maturation of thymocyte subpopulations in late developmental stages and suggests that IL-7R expression on alpha beta T cells suppresses development of other cell lineages in thymus.
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