Sin1 regulates Treg-cell development but is not required for T-cell growth and proliferation.
Sin1 regulates Treg-cell development but is not required for T-cell growth and proliferation.
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DOI：
10.1002/eji.201142066
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发表时间：
2012-06
影响因子：
5.4
通讯作者：
Su, Bing
中科院分区：
文献类型：
--
作者：
Chang, Xing;Lazorchak, Adam S.;Liu, Dou;Su, Bing
哺乳动物SIN1在丝裂原活化蛋白激酶(MAPK)和哺乳动物雷帕霉素靶标(MTOR)信号的调节中起关键作用。SIN1是mTOR复合体(MTORC)2的重要组成部分。SIN1和mTORC2在T细胞中的功能尚不清楚。在这里，我们使用在造血系统中缺乏SIN1的小鼠来研究SIN1在T细胞中的功能。在T细胞的发育和激活过程中，SIN1缺乏阻断依赖mTORC2的Akt的磷酸化。SIN1缺陷的T细胞表现出正常的胸腺细胞密度和双阴性、双阳性和单阳性的CD4和CD8胸腺细胞百分比。SIN1缺乏不会损害T细胞受体(TCR)诱导的生长和增殖以及正常的CD4+辅助细胞分化。然而，SIN1缺乏导致胸腺中Foxp3+自然T调节(NTreg)细胞比例增加。我们的研究表明，抑制mTOR而不是丧失β功能可以促进体外培养的T细胞对转化生长因子-SIN1的依赖分化。我们的结果表明，SIN1和mTORC2对T细胞的发育和激活是必不可少的，但在自然Treg细胞分化中起作用。
Mammalian Sin1 plays key roles in the regulation of mitogen activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling. Sin1 is an essential component of mTOR complex (mTORC) 2. The function of Sin1 and mTORC2 remains largely unknown in T cells. Here we investigate Sin1 function in T cells using mice which lack Sin1 in the hematopoietic system. Sin1 deficiency blocks the mTORC2 dependent Akt phosphorylation in T cells during development and activation. Sin1 deficient T cells exhibit normal thymic cellularity and percentages of double negative, double positive and single positive CD4 and CD8 thymocytes. Sin1 deficiency does not impair T cell receptor (TCR) induced growth and proliferation, and normal CD4+ helper cell differentiation. However Sin1 deficiency results in an increased proportion of Foxp3+ natural T regulatory (nTreg) cells in the thymus. We show that the TGF-β dependent differentiation of CD4+ T cells in vitro is enhanced by the inhibition of mTOR but not loss of Sin1 function. Our results reveal that Sin1 and mTORC2 are dispensable for the development and activation of T cells but play a role in natural Treg cell differentiation.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
32.4
作者：
Chang X;Liu F;Wang X;Lin A;Zhao H;Su B
通讯作者：
Su B
影响因子：
5.3
作者：
Brunet, A;Park, J;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
64.8
作者：
Araki, Koichi;Turner, Alexandra P.;Shaffer, Virginia Oliva;Gangappa, Shivaprakash;Keller, Susanne A.;Bachmann, Martin F.;Larsen, Christian P.;Ahmed, Rafi
通讯作者：
Ahmed, Rafi
影响因子：
16
作者：
Lazorchak AS;Liu D;Facchinetti V;Di Lorenzo A;Sessa WC;Schatz DG;Su B
通讯作者：
Su B