特里夫
锡克
整合素αM
先天免疫系统
细胞生物学
信号转导衔接蛋白
磷酸化
整合素
信号转导
泛素连接酶
Toll样受体
化学
受体
生物
泛素
免疫学
酪氨酸激酶
免疫系统
生物化学
基因
作者
Chaofeng Han,Jing Jin,Sheng Xu,Haibo Li,Nan Li,Xuetao Cao
摘要
Integrins are critical for the migration and function of leukocytes in inflammation. However, the interaction between integrin alpha(M) (CD11b), which has high expression in monocytes and macrophages, and Toll-like receptor (TLR)-triggered innate immunity remains unclear. Here we report that CD11b deficiency enhanced TLR-mediated responses in macrophages, rendering mice more susceptible to endotoxin shock and Escherichia coli-caused sepsis. CD11b was activated by TLR-triggered phosphatidylinositol 3-OH kinase (PI(3)K) and the effector RapL and fed back to inhibit TLR signaling by activating the tyrosine kinases Src and Syk. Syk interacted with and induced tyrosine phosphorylation of MyD88 and TRIF, which led to degradation of these adaptor molecules by the E3 ubiquitin ligase Cbl-b. Thus, TLR-triggered, active CD11b integrin engages in crosstalk with the MyD88 and TRIF pathways and subsequently inhibits TLR signaling in innate immune responses.
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