Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk
Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk
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DOI：
10.1038/ni.2015
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发表时间：
2011-05-01
影响因子：
30.5
通讯作者：
Cao, Xuetao
中科院分区：
文献类型：
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作者：
Liu, Xingguang;Zhan, Zhenzhen;Cao, Xuetao
通过Toll样受体(Toll-like Receptor，TLRs)充分激活天然免疫的分子机制仍未完全阐明。除了经典的抗原提呈功能外，主要组织相容性复合体(MHC)II类分子还可能介导反向信号。在这里，我们报告了MHC II类分子的缺陷减弱了TLR触发的巨噬细胞和树突状细胞中促炎症细胞因子和I型干扰素的产生，从而保护小鼠免受内毒素休克。细胞内MHC II类分子通过共刺激分子CD40与酪氨酸激酶BTK相互作用，并维持BTK的激活，但细胞表面MHC II类分子不能。然后，BTK与接头分子MyD88和TRIF相互作用，从而促进TLR信号转导。因此，细胞内的MHC II类分子可以作为适配器，促进TLR触发的先天免疫反应的充分激活。
The molecular mechanisms involved in the full activation of innate immunity achieved through Toll-like receptors (TLRs) remain to be fully elucidated. In addition to their classical antigen-presenting function, major histocompatibility complex (MHC) class II molecules might mediate reverse signaling. Here we report that deficiency in MHC class II attenuated the TLR-triggered production of proinflammatory cytokines and type I interferon in macrophages and dendritic cells, which protected mice from endotoxin shock. Intracellular MHC class II molecules interacted with the tyrosine kinase Btk via the costimulatory molecule CD40 and maintained Btk activation, but cell surface MHC class II molecules did not. Then, Btk interacted with the adaptor molecules MyD88 and TRIF and thereby promoted TLR signaling. Therefore, intracellular MHC class II molecules can act as adaptors, promoting full activation of TLR-triggered innate immune responses.