CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.
CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.
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DOI：
10.1016/j.immuni.2008.08.018
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发表时间：
2008-11-14
期刊：
影响因子：
32.4
通讯作者：
Pucillo CE
中科院分区：
文献类型：
--
作者：
Gri G;Piconese S;Frossi B;Manfroi V;Merluzzi S;Tripodo C;Viola A;Odom S;Rivera J;Colombo MP;Pucillo CE
CD4+CD25+T调节细胞(Tregs)在抑制免疫反应中发挥核心作用，从而诱导免疫耐受并控制可导致自身免疫的持续性免疫反应。在这里，我们探索Tregs是否也在控制肥大细胞(MC)的即刻超敏反应中发挥作用。Tregs通过细胞与MCs之间的OX40-OX40L相互作用直接抑制依赖FcεRI的MCs脱颗粒。MCs显示cAMP水平升高，钙内流减少，与PLC-γ2或细胞内钙释放无关。MCs上cAMP的拮抗作用可逆转Tregs恢复正常钙反应和脱颗粒的抑制作用。重要的是，体内Tregs的耗尽或失活会导致过敏反应的增强。Tregs和MCs之间的串扰定义了一种以前未被认识的控制MCs脱颗粒的机制。这种相互作用的丧失可能导致过敏反应的严重程度。
CD4+CD25+ T regulatory cells (Tregs) play a central role in the suppression of immune responses thus serving to induce tolerance and to control persistent immune responses that can lead to autoimmunity. Here we explore if Tregs also play a role in controlling the immediate hypersensitivity response of mast cells (MCs). Tregs directly inhibit the FcεRI-dependent degranulation of MCs through cell-cell contact involving OX40-OX40L interactions between Tregs and MCs, respectively. MCs show increased cAMP levels and reduced Ca2+ influx, independent of PLC-γ2 or Ca2+ release from intracellular stores. Antagonism of cAMP in MCs reverses the inhibitory effects of Tregs restoring normal Ca2+ responses and degranulation. Importantly, the in vivo depletion or inactivation of Tregs causes enhancement of the anaphylactic response. The demonstrated cross-talk between Tregs and MCs defines a previously unrecognized mechanism controlling MCs degranulation. Loss of this interaction may contribute to the severity of allergic responses.
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影响因子：
5.4
作者：
Hoshino, A;Tanaka, Y;Okumura, K
通讯作者：
Okumura, K
影响因子：
32.4
作者：
Mempel, Thorsten R.;Pittet, Mikael J.;von Andrian, Ulrich H.
通讯作者：
von Andrian, Ulrich H.
影响因子：
14.2
作者：
Karagiannidis, C;Akdis, M;Schmidt-Weber, CB
通讯作者：
Schmidt-Weber, CB
通过B细胞表达的OX40L共刺激足以确定体内原代CD4细胞膨胀和Th2细胞因子分泌的程度。
影响因子：
15.3
作者：
Linton, PJ;Bautista, B;Biederman, E;Bradley, ES;Harbertson, J;Kondrack, RM;Padrick, RC;Bradley, LM
通讯作者：
Bradley, LM
影响因子：
15.3
作者：
Murata, K;Ishii, N;Takano, H;Miura, S;Ndhlovu, L C;Nose, M;Noda, T;Sugamura, K
通讯作者：
Sugamura, K