Rapid and Efficient Generation of Regulatory T Cells to Commensal Antigens in the Periphery.
Rapid and Efficient Generation of Regulatory T Cells to Commensal Antigens in the Periphery.
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DOI：
10.1016/j.celrep.2016.08.092
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发表时间：
2016-09-27
期刊：
影响因子：
8.8
通讯作者：
Hsieh CS
中科院分区：
文献类型：
--
作者：
Nutsch K;Chai JN;Ai TL;Russler-Germain E;Feehley T;Nagler CR;Hsieh CS
共生细菌塑造肠道耐受所需的结肠调节性T细胞（Treg）群体。然而，人们对这一过程知之甚少。在这里，我们使用表达结肠Treg TCR的幼稚结肠反应性转基因T细胞的转移来研究正常宿主中的外周Treg（pTreg）细胞发育。我们发现T细胞主要在远端肠系膜淋巴结中被激活。Treg细胞诱导是快速的，在转移后一周产生>40%的Foxp3+细胞。与之前的报道相反，Foxp3+细胞经历了最多的细胞分裂，表明pTreg细胞生成可能是幼稚T细胞活化的主要结果。此外，Notch2依赖性而非Batf3依赖性树突状细胞参与Treg细胞选择。最后，Foxp3中CNS1区域的缺失和TGFβ受体信号传导的阻断都不能完全消除Foxp3的诱导作用。因此，这些数据表明，pTreg细胞对大肠杆菌的选择是快速、稳健的，并且可以由TGFβ非依赖性信号指定。
Commensal bacteria shape the colonic regulatory T (Treg) cell population required for intestinal tolerance. However, little is known about this process. Here, we use the transfer of naïve commensal-reactive transgenic T cells expressing colonic Treg TCRs to study peripheral Treg (pTreg) cell development in normal hosts. We found that T cells were activated primarily in the distal mesenteric lymph node. Treg cell induction was rapid, generating >40% Foxp3+ cells one week post-transfer. Contrary to prior reports, Foxp3+ cells underwent the most cell divisions, demonstrating that pTreg cell generation can be the dominant outcome from naïve T cell activation. Moreover, Notch2-dependent but not Batf3-dependent, dendritic cells were involved in Treg cell selection. Finally, neither deletion of the CNS1 region in Foxp3, nor blockade of TGFβ-receptor signaling, completely abrogated Foxp3 induction. Thus, these data show that pTreg cell selection to commensal bacteria is rapid, robust, and may be specified by TGFβ-independent signals.
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影响因子：
3.7
作者：
Akimova T;Beier UH;Wang L;Levine MH;Hancock WW
通讯作者：
Hancock WW
影响因子：
32.4
作者：
Haribhai D;Williams JB;Jia S;Nickerson D;Schmitt EG;Edwards B;Ziegelbauer J;Yassai M;Li SH;Relland LM;Wise PM;Chen A;Zheng YQ;Simpson PM;Gorski J;Salzman NH;Hessner MJ;Chatila TA;Williams CB
通讯作者：
Williams CB
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
32.4
作者：
Gorelik, L;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
4.4
作者：
Gottschalk, Rachel A.;Corse, Emily;Allison, James P.
通讯作者：
Allison, James P.