IL-2, -7, and -15, but not thymic stromal lymphopoeitin, redundantly govern CD4+Foxp3+ regulatory T cell development.
IL-2, -7, and -15, but not thymic stromal lymphopoeitin, redundantly govern CD4+Foxp3+ regulatory T cell development.
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DOI：
10.4049/jimmunol.181.5.3285
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发表时间：
2008-09-01
期刊：
影响因子：
--
通讯作者：
Farrar MA
中科院分区：
文献类型：
--
作者：
Vang KB;Yang J;Mahmud SA;Burchill MA;Vegoe AL;Farrar MA
由于γ c −/−小鼠缺乏调节性T细胞（Treg），因此调节性T细胞（Treg）发育需要常见的γ链（γ c）受体依赖性细胞因子。然而，目前还不清楚哪些γ c依赖性细胞因子参与了这一过程。此外，TSLP也被认为在Treg发育中发挥作用。在此，我们证明胸腺中发育的CD4 + Foxp3 + T细胞表达IL 2R β、IL 4R α、IL 7R α、IL 15 R α和IL 21 R α链，但不表达IL 9R α或TSLPR α链。此外，通过监测STAT5磷酸化测定，只有IL 2，以及程度小得多的IL 7和IL 15，能够在CD4 + Foxp3 + T细胞中转导信号。同样，IL 2、IL 7和IL 15，而不是TSLP，能够在体外诱导CD4 + CD25 + Foxp3 −胸腺Treg祖细胞转化为CD4 + Foxp3+成熟Treg。为了更详细地研究这个问题，我们产生了IL 2 R β −/− x IL 7 R α −/−和IL 2 R β −/− x IL 4 R α −/−小鼠。我们发现，IL 2 R β −/− x IL 7 R α −/−小鼠缺乏T细胞，从而重现了在γ c −/−小鼠中观察到的表型;相反，在IL 2 R β −/− x IL 4 R α −/−小鼠中观察到的表型与在IL 2 R β −/−小鼠中观察到的表型相当。最后，我们观察到来自IL 2 −/−和IL 2 R β −/−小鼠的TcR显示IL 7 R α和IL 15 R α链的表达升高。将IL 2添加到来自IL 2 −/−小鼠的TcR中导致这些受体的快速下调。综上所述，我们的结果表明，IL 2在Treg发育中起主要作用，但在其缺失的情况下，IL 7 R α和IL 15 R α链上调，并允许IL 7和IL 15部分补偿IL 2的损失。
Common γ chain (γc)-receptor dependent cytokines are required for regulatory T cell (Treg) development as γc−/− mice lack Tregs. However, it is unclear which γc-dependent cytokines are involved in this process. Furthermore, TSLP has also been suggested to play a role in Treg development. Herein, we demonstrate that developing CD4+Foxp3+ Tregs in the thymus express the IL2Rβ, IL4Rα, IL7Rα, IL15Rα and IL21Rα chains, but not the IL9Rα or TSLPRα chains. Moreover, only IL2, and to a much lesser degree IL7 and IL15, were capable of transducing signals in CD4+Foxp3+ Tregs as determined by monitoring STAT5 phosphorylation. Likewise, IL2, IL7 and IL15, but not TSLP, were capable of inducing the conversion of CD4+CD25+Foxp3− thymic Treg progenitors into CD4+Foxp3+ mature Tregs in vitro. To examine this issue in more detail we generated IL2Rβ−/− x IL7Rα−/− and IL2Rβ−/− x IL4Rα−/− mice. We found that IL2Rβ−/− x IL7Rα−/− mice were devoid of Tregs thereby recapitulating the phenotype observed in γc−/− mice; in contrast, the phenotype observed in IL2Rβ−/− x IL4Rα−/− mice was comparable to that seen in IL2Rβ−/− mice. Finally, we observed that Tregs from both IL2−/− and IL2Rβ−/− mice show elevated expression of IL7Rα and IL15Rα chains. Addition of IL2 to Tregs from IL2−/− mice led to rapid downregulation of these receptors. Taken together, our results demonstrate that IL2 plays the predominant role in Treg development, but that in its absence the IL7Rα and IL15Rα chains are upregulated and allow for IL7 and IL15 to partially compensate for loss of IL2.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
CD127表达与FOXP3和人类CD4+ T Reg细胞的抑制功能成反比。
DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Burchill, Matthew A.;Yang, Jianying;Farrar, Michael A.
通讯作者：
Farrar, Michael A.
影响因子：
30.5
作者：
Aschenbrenner, Katharina;D'Cruz, Louise M.;Klein, Ludger
通讯作者：
Klein, Ludger
影响因子：
32.4
作者：
Lio, Chan-Wang Joaquim;Hsieh, Chyi-Song
通讯作者：
Hsieh, Chyi-Song