Self-antigen-driven activation induces instability of regulatory T cells during an inflammatory autoimmune response.
Self-antigen-driven activation induces instability of regulatory T cells during an inflammatory autoimmune response.
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DOI：
10.1016/j.immuni.2013.10.016
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发表时间：
2013-11-14
期刊：
影响因子：
32.4
通讯作者：
Bluestone, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Bailey-Bucktrout, Samantha L.;Martinez-Llordella, Marc;Zhou, Xuyu;Anthony, Bryan;Rosenthal, Wendy;Luche, Herve;Fehling, Hans J.;Bluestone, Jeffrey A.
稳定的Foxp 3表达对于调节性T（Treg）细胞功能至关重要。我们观察到，中枢神经系统（CNS）中抗原驱动的激活和炎症选择性地促进了在实验性自身免疫性脑炎诱导前表达高Foxp 3水平的自身反应性Treg细胞中Foxp 3的不稳定性。在反应的诱导阶段，在Foxp 3基因座中具有去甲基化Treg细胞特异性去甲基化区域的Treg细胞下调发炎CNS中的Foxp 3转录。稳定的Foxp 3表达在群体水平上随着炎症的消退而恢复，或者在抗原引发阶段期间通过IL-2：抗IL-2复合物治疗来挽救。因此，一个完全定型的自身抗原特异性Treg细胞亚群在炎症性自身免疫应答期间丢失Foxp 3表达，并且可能参与自身免疫的不充分控制。这些结果对Treg细胞疗法具有重要意义，并对体内自身反应性CD 4 + T细胞效应子应答期间Treg细胞网络的动态提供了见解。
Stable Foxp3 expression is crucial for regulatory T (Treg) cell function. We observed that antigen-driven activation and inflammation in the central nervous system (CNS) promoted Foxp3 instability selectively in the autoreactive Treg cells that expressed high Foxp3 levels before experimental autoimmune encephalitis induction. Treg cells with a demethylated Treg cell-specific demethylated region in the Foxp3 locus down-regulated Foxp3 transcription in the inflamed CNS during the induction phase of the response. Stable Foxp3 expression returned at the population level with the resolution of inflammation or was rescued by IL-2:anti-IL-2 complex treatment during the antigen priming phase. Thus, a subset of fully committed self-antigen-specific Treg cells lost Foxp3 expression during an inflammatory autoimmune response and may be involved in inadequate control of autoimmunity. These results have important implications for Treg cell therapies, and give insights into the dynamics of the Treg cell network during auto-reactive CD4+ T cell effector responses in vivo.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
30.5
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
通讯作者：
Rudensky, AY
DOI：
10.4049/jimmunol.0900691
发表时间：
2009-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
O'Gorman WE;Dooms H;Thorne SH;Kuswanto WF;Simonds EF;Krutzik PO;Nolan GP;Abbas AK
通讯作者：
Abbas AK
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
影响因子：
100.3
作者：
Huehn, Jochen;Polansky, Julia K.;Hamann, Alf
通讯作者：
Hamann, Alf