调节性T细胞通过淋巴细胞激活基因-3与II类主要组织相容性复合体的结合来抑制树突状细胞。
Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II.
作者信息
Liang Bitao, Workman Craig, Lee Janine, Chew Claude, Dale Benjamin M, Colonna Lucrezia, Flores Marcella, Li Nianyu, Schweighoffer Edina, Greenberg Steven, Tybulewicz Victor, Vignali Dario, Clynes Raphael
机构信息
Departments of Microbiology, Pharmacology and Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
出版信息
J Immunol. 2008 May 1;180(9):5916-26. doi: 10.4049/jimmunol.180.9.5916.
Lymphocyte activation gene-3 (LAG-3) is a CD4-related transmembrane protein expressed by regulatory T cells that binds MHC II on APCs. It is shown in this study that during Treg:DC interactions, LAG-3 engagement with MHC class II inhibits DC activation. MHC II cross-linking by agonistic Abs induces an ITAM-mediated inhibitory signaling pathway, involving FcgammaRgamma and ERK-mediated recruitment of SHP-1 that suppresses dendritic cell maturation and immunostimulatory capacity. These data reveal a novel ITAM-mediated inhibitory signaling pathway in DCs triggered by MHC II engagement of LAG-3, providing a molecular mechanism in which regulatory T cells may suppress via modulating DC function.
淋巴细胞激活基因-3（LAG-3）是一种与CD4相关的跨膜蛋白，由调节性T细胞表达，可与抗原呈递细胞（APC）上的MHC II结合。本研究表明，在调节性T细胞与树突状细胞（DC）相互作用过程中，LAG-3与II类MHC结合会抑制DC激活。激动性抗体介导的MHC II交联会诱导ITAM介导的抑制性信号通路，该通路涉及FcγRγ和ERK介导的SHP-1募集，从而抑制树突状细胞成熟和免疫刺激能力。这些数据揭示了由LAG-3与MHC II结合触发的DC中一种新的ITAM介导的抑制性信号通路，为调节性T细胞可能通过调节DC功能进行抑制提供了一种分子机制。
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