Engagement of TLR2 does not reverse the suppressor function of mouse regulatory T cells, but promotes their survival.
Engagement of TLR2 does not reverse the suppressor function of mouse regulatory T cells, but promotes their survival.
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DOI：
10.4049/jimmunol.0901465
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发表时间：
2009-10-01
期刊：
影响因子：
--
通讯作者：
Shevach EM
中科院分区：
文献类型：
--
作者：
Chen Q;Davidson TS;Huter EN;Shevach EM
TLR是一类由先天免疫系统的细胞使用的保守模式识别受体。最近的研究已经证明TLR在人和小鼠T细胞上的表达提高了TLR在获得性免疫中发挥直接作用的可能性。TLR 2主要由细菌壁组分激活，包括肽聚糖和脂蛋白。几项研究表明，小鼠调节性T细胞（Treg）表达TLR 2，并声称合成配体与TLR 2的结合逆转了它们的抑制功能。相反，在TLR 2参与人Treg后观察到Treg功能的增强。我们已经重新检查了TLR 2在小鼠Treg上的表达和功能，所述小鼠Treg从Foxp 3-GFP敲除小鼠中纯化。通过TLR 2激动剂合成细菌脂蛋白（BLP）Pam 3CSK 4连接TLR 2增强了常规T细胞和Treg在不存在APC的情况下响应TLR刺激的增殖应答。用Pam 3CSK 4处理Foxp 3 + Treg在体外或体内不改变它们的抑制功能，并且不降低它们的Foxp 3表达水平。TLR 2刺激Treg的另一个作用是诱导Bcl-xL，导致体外存活率提高。用TLR 2激动剂治疗小鼠增强了体内Treg抗原驱动的增殖，但没有消除其抑制EAE发展的能力。开发选择性刺激Treg上的TLR 2的方法可能会导致治疗自身免疫性疾病的新方法。
TLRs are a class of conserved pattern recognition receptors that are used by cells of the innate immune system. Recent studies have demonstrated the expression of TLRs on both human and mouse T cells raising the possibility that TLRs play a direct role in adaptive immunity. TLR2 is activated primarily by bacterial wall components including peptidoglycan and lipoproteins. Several studies have shown that mouse regulatory T (Treg) express TLR2 and claimed that engagement of TLR2 by synthetic ligands reversed their suppressive function. In contrary, enhancement of Treg function was observed following engagement of TLR2 on human Treg. We have re-examined the expression and function of TLR2 on mouse Treg purified from Foxp3-GFP knock in mice. TLR2 ligation by TLR2 agonist, the synthetic bacterial lipoprotein (BLP) Pam3CSK4, enhanced the proliferative responses of both conventional T cells and Treg in response to TLR stimulation in the absence of APC. Treatment of Foxp3+ Treg with Pam3CSK4 did not alter their suppressive function in vitro or in vivo and did not reduce their level of Foxp3 expression. An additional effect of TLR2 stimulation of Treg was induction of Bcl-xL resulting in enhanced survival in vitro. Treatment of mice with the TLR2 agonist enhanced the antigen-driven proliferation of Treg in vivo, but did not abolish their ability to suppress the development of EAE. Development of methods to selectively stimulate TLR2 on Treg may lead to a novel approaches for the treatment of autoimmune diseases.
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