Development of regulatory T cells requires IL-7Rα stimulation by IL-7 or TSLP
Development of regulatory T cells requires IL-7Rα stimulation by IL-7 or TSLP
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DOI：
10.1182/blood-2008-02-137414
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发表时间：
2008-10-15
期刊：
影响因子：
20.3
通讯作者：
Durum, Scott K.
中科院分区：
文献类型：
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作者：
Mazzucchelli, Renata;Hixon, Julie A.;Durum, Scott K.
白细胞介素7(IL-7)是一种由基质细胞产生的细胞因子，对胸腺发育和大多数主要T细胞亚群的外周稳态是必需的。我们通过分析IL-7Rα(-/-)小鼠来检验调节性T(Treg)细胞是否也需要IL-7途径。我们观察到具有Treg表面表型(CD4、CD25、GITR(糖皮质激素诱导的肿瘤坏死因子样受体)、CD45RB、CD62L、CD103)或细胞内标志(细胞毒性T淋巴细胞相关抗原-4、CTLA-4和叉头盒转录因子3、Foxp3)的细胞显著减少。在IL-7Rα(-/-)淋巴组织中几乎没有Foxp3转录本，也没有检测到Treg细胞抑制活性。已知的IL-7Rα的配体有两种：IL-7本身和胸腺基质淋巴生成素(TSLP)。令人惊讶的是，缺乏IL-7或其他TSLP受体链(TSLPR)的小鼠产生了相对正常数量的Treg细胞。IL-7和TSLP受体的联合缺失大大减少了胸腺中Treg细胞的发育，但对成熟的外周Treg细胞的生存并不是必需的。我们得出结论，与其他T细胞一样，Treg细胞需要来自IL-7受体的信号，但与其他T细胞不同，Treg细胞不需要IL-7本身，因为至少在Treg细胞发育过程中IL-7和TSLP的作用部分重叠。
Interleukin-7 (IL-7), a cytokine produced by stromal cells, is required for thymic development and peripheral homeostasis of most major subsets of T cells. We examined whether regulatory T (Treg) cells also required the IL-7 pathway by analyzing IL-7R alpha(-/-) mice. We observed a striking reduction in cells with the Treg surface phenotype (CD4, CD25, GITR (glucocorticoid-induced tumor necrosis factor [TNF]-like receptor), CD45RB, CD62L, CD103) or intracellular markers (cytotoxic T-lymphocyte associated antigen-4, CTLA-4, and forkhead box transcription factor 3, Foxp3). Foxp3 transcripts were virtually absent in IL-7R alpha(-/-) lymphoid tissues, and no Treg cell suppressive activity could be detected. There are 2 known ligands for IL-7R alpha: IL-7 itself and thymic stromal lymphopoietin (TSLP). Surprisingly, mice deficient in IL-7 or the other chain of the TSLP receptor (TSLPR) developed relatively normal numbers of Treg cells. Combined deletion of IL-7 and TSLP receptor greatly reduced Treg cell development in the thymus but was not required for survival of mature peripheral Treg cells. We conclude that Treg cells, like other T cells, require signals from the IL-7 receptor, but unlike other T cells, do not require IL-7 itself because of at least partially overlapping actions of IL-7 and TSLP for development of Treg cells.