Interleukin-7 receptor controls development and maturation of late stages of thymocyte subpopulations
Interleukin-7 receptor controls development and maturation of late stages of thymocyte subpopulations
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DOI：
10.1073/pnas.1219242110
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发表时间：
2013-01-08
影响因子：
11.1
通讯作者：
Ikuta, Koichi
中科院分区：
文献类型：
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作者：
Tani-ichi, Shizue;Shimba, Akihiro;Ikuta, Koichi
白细胞介素（IL）-7是T淋巴细胞发育和稳态所必需的细胞因子。然而，关于IL-7受体α链（IL-7 R α）在T细胞发育后期的作用知之甚少。为了解决这个问题，我们建立了IL-7 R α-floxed小鼠，并将它们与CD 4-Cre转基因小鼠杂交。所得IL-7 R条件性敲除（IL-7 RcKO）小鼠在胸腺中表现出CD 8单阳性（SP）T细胞、调节性T细胞（T细胞）和自然杀伤T（NKT）细胞的显著减少。成熟的CD 4 SP和CD 8 SP胸腺细胞的比例和增殖均降低，但不影响Runx的表达。此外，糖皮质激素诱导的TNF受体的表达在CD 4SP和CD 8 SP胸腺细胞中减少，并且在CD 8 SP胸腺细胞中CD 5的表达减少。IL-7 RcKO小鼠还显示Treg和NKT细胞增殖受损以及NKT细胞成熟抑制。Bcl-2表达在CD 4SP和CD 8 SP胸腺细胞中降低，但在TcB和NKT细胞中不降低，并且引入Bcl-2转基因挽救了CD 8 SP胸腺细胞的频率和CD 5表达。此外，IL-7 RcKO小鼠胸腺中B细胞数量显著增加，γ δ T细胞和树突状细胞数量较少。总体而言，这项研究表明，IL-7 R α差异控制胸腺细胞亚群的发育和成熟在发育后期阶段，并表明，IL-7 R的表达α β T细胞抑制其他细胞系在胸腺的发展。
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.