The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells
The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells
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DOI：
10.1038/ni.1674
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发表时间：
2009-01-01
影响因子：
30.5
通讯作者：
Grogan, Jane L.
中科院分区：
文献类型：
--
作者：
Yu, Xin;Harden, Kristin;Grogan, Jane L.
在这里，我们已经确定了一个表面蛋白，TIGIT，含有免疫球蛋白可变结构域，跨膜结构域和免疫受体酪氨酸为基础的抑制基序，表达在调节，记忆和活化的T细胞。在树突细胞上表达的脊髓灰质炎病毒受体以高亲和力结合TIGIT。TIGIT-Fc融合蛋白在体外抑制T细胞活化，并且这依赖于树突细胞的存在。脊髓灰质炎病毒受体与人树突状细胞上的TIGIT的结合增强了白细胞介素10的产生并减少了白细胞介素12 p40的产生。在人记忆T细胞中用小干扰RNA敲低TIGIT不影响T细胞应答。TIGIT-Fc抑制野生型但非白细胞介素10缺陷小鼠的迟发型超敏反应。我们的数据表明TIGIT通过结合脊髓灰质炎病毒受体并调节树突状细胞的细胞因子产生来发挥免疫抑制作用。
Here we have identified a surface protein, TIGIT, containing an immunoglobulin variable domain, a transmembrane domain and an immunoreceptor tyrosine-based inhibitory motif that was expressed on regulatory, memory and activated T cells. Poliovirus receptor, which is expressed on dendritic cells, bound TIGIT with high affinity. A TIGIT-Fc fusion protein inhibited T cell activation in vitro, and this was dependent on the presence of dendritic cells. The binding of poliovirus receptor to TIGIT on human dendritic cells enhanced the production of interleukin 10 and diminished the production of interleukin 12p40. Knockdown of TIGIT with small interfering RNA in human memory T cells did not affect T cell responses. TIGIT-Fc inhibited delayed-type hypersensitivity reactions in wild-type but not interleukin 10-deficient mice. Our data suggest that TIGIT exerts immunosuppressive effects by binding to poliovirus receptor and modulating cytokine production by dendritic cells.