整合素
热休克蛋白
细胞生物学
生物
热休克蛋白90
T细胞
高内皮静脉
免疫系统
免疫学
细胞
生物化学
基因
作者
Changdong Lin,Youhua Zhang,Kun Zhang,Yajuan Zheng,Ling Lu,Haishuang Chang,Hui Ye,Yanrong Yang,YaoYing Wan,ShiHui Wang,Mao Yuan,ZhanJun Yan,RongGuang Zhang,Yongning He,Gaoxiang Ge,Dianqing Wu,Jianfeng Chen
出处
期刊:Immunity
[Elsevier]
日期:2019-01-01
卷期号:50 (1): 137-151.e6
被引量:64
标识
DOI:10.1016/j.immuni.2018.11.013
摘要
Fever is an evolutionarily conserved response that confers survival benefits during infection. However, the underlying mechanism remains obscure. Here, we report that fever promoted T lymphocyte trafficking through heat shock protein 90 (Hsp90)-induced α4 integrin activation and signaling in T cells. By inducing selective binding of Hsp90 to α4 integrins, but not β2 integrins, fever increased α4-integrin-mediated T cell adhesion and transmigration. Mechanistically, Hsp90 bound to the α4 tail and activated α4 integrins via inside-out signaling. Moreover, the N and C termini of one Hsp90 molecule simultaneously bound to two α4 tails, leading to dimerization and clustering of α4 integrins on the cell membrane and subsequent activation of the FAK-RhoA pathway. Abolishment of Hsp90-α4 interaction inhibited fever-induced T cell trafficking to draining lymph nodes and impaired the clearance of bacterial infection. Our findings identify the Hsp90-α4-integrin axis as a thermal sensory pathway that promotes T lymphocyte trafficking and enhances immune surveillance during infection.
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