Block of both TGF-β and IL-2 signaling impedes Neurophilin-1(+) regulatory T cell and follicular regulatory T cell development.
Block of both TGF-β and IL-2 signaling impedes Neurophilin-1(+) regulatory T cell and follicular regulatory T cell development.
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阻断 TGF-β 和 IL-2 信号传导会阻碍 Neurophilin-1( ) 调节性 T 细胞和滤泡调节性 T 细胞的发育
DOI：
10.1038/cddis.2016.348
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发表时间：
2016-10-27
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
了解导致自身免疫的机制对于确定潜在的治疗途径至关重要。在这方面，已经有相当多的努力来研究转化生长因子-β和IL-2在功能调节T细胞中的相互作用。我们利用了dnTGF-βRII IL2ra−/−(简称IL2ra−/−TG)小鼠模型，该模型允许一种直接的机制方法来确定转化生长因子-β和IL-2在Treg发生中的相对作用。IL2ra−/−Tg小鼠在3-4周龄时自发发生多器官自身免疫性疾病，致病T细胞增多，生发中心反应增强。重要的是，IL2ra−/−TG小鼠外周血树突状细胞表现出激活的Th1型稳定表型和正常的体外抑制功能，而胸腺Treg细胞增加但表现为抑制功能降低。有趣的是，Il2ra−/−转基因小鼠的胸腺和外周Treg细胞都不含有Neuropilin-1+或PD-1hi表型，导致卵泡调节性T细胞发育缺陷。这种缺陷的TFR发育导致滤泡辅助性T细胞增加，生发中心反应增强，浆细胞浸润增加。这些数据表明，转化生长因子-β和IL-2在Treg细胞的产生、激活和稳定以及随后向TfR细胞的发展中起着重要的协同作用。
Understanding the mechanisms that lead to autoimmunity is critical for defining potential therapeutic pathways. In this regard there have been considerable efforts in investigating the interacting roles of TGF-β and IL-2 on the function regulatory T cells. We have taken advantage of dnTGF-βRII Il2ra−/− (abbreviated as Il2ra−/−Tg) mouse model, which allows a direct mechanistic approach to define the relative roles of TGF-β and IL-2 on Treg development. Il2ra−/−Tg mice spontaneously developed multi-organ autoimmune diseases with expansion of pathogenic T cells and enhanced germinal center response at 3–4 weeks of age. Importantly, peripheral Treg cells from Il2ra−/−Tg mice demonstrated an activated Th1-like stable phenotype and normal in vitro suppressive function, while thymus Treg increased but manifested decreased suppressive function. Interestingly, neither thymus nor peripheral Treg cells of Il2ra−/−Tg mice contained Neuropilin-1+ or PD-1hi phenotype, resulting in defective follicular regulatory T (Tfr) cell development. Such defective Tfr development led to elevated follicular T helper cells, enhanced germinal center responses and increased plasma cell infiltration. These data demonstrate an important synergetic role of TGF-β and IL-2 in the generation, activation and stability of Treg cells, as well as their subsequent development into Tfr cells.
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影响因子：
--
作者：
Elkord E;Abd Al Samid M;Chaudhary B
通讯作者：
Chaudhary B
影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
DOI：
10.1159/000289201
发表时间：
2010
期刊：
Current directions in autoimmunity
影响因子：
--
作者：
Chen X;Oppenheim JJ
通讯作者：
Oppenheim JJ
影响因子：
32.4
作者：
Gorelik, L;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
12.8
作者：
Aoki, Christopher A.;Roifman, Chaim M.;Gershwin, M. Eric
通讯作者：
Gershwin, M. Eric