Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and α4 Integrins
Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and α4 Integrins
复制标题
发烧通过涉及热休克蛋白 90 和 α 4 整合素的热感觉通路促进 T 淋巴细胞运输
DOI：
10.1016/j.immuni.2018.11.013
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发表时间：
2019-01-15
期刊：
影响因子：
32.4
通讯作者：
Chen, JianFeng
中科院分区：
文献类型：
--
作者：
Lin, ChangDong;Zhang, YouHua;Chen, JianFeng
发热是一种进化上保守的反应，在感染期间赋予生存益处。然而，其潜在机制仍不清楚。在这里，我们报告说，发热促进T淋巴细胞运输通过热休克蛋白90（HSP 90）诱导α 4整合素活化和信号在T细胞。通过诱导热休克蛋白90选择性结合α 4整合素，而不是β 2整合素，发热增加α 4-整合素介导的T细胞粘附和迁移。从机制上讲，Hsp 90与α 4尾结合，并通过由内而外的信号传导激活α 4整联蛋白。此外，一个Hsp 90分子的N和C末端同时结合到两个α 4尾，导致α 4整联蛋白在细胞膜上的二聚化和聚集以及随后FAK-RhoA途径的激活。Hsp 90-α 4相互作用的消除抑制了发热诱导的T细胞向引流淋巴结的运输，并损害了细菌感染的清除。我们的研究结果确定了热休克蛋白90-α 4-]整合素轴作为一个热感觉途径，促进T淋巴细胞运输和增强免疫监视感染期间。
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 alpha 4 integrin activation and signaling in T cells. By inducing selective binding of Hsp90 to alpha 4 integrins, but not beta 2 integrins, fever increased alpha 4-integrin-mediated T cell adhesion and transmigration. Mechanistically, Hsp90 bound to the alpha 4 tail and activated alpha 4 integrins via inside-out signaling. Moreover, the N and C termini of one Hsp90 molecule simultaneously bound to two alpha 4 tails, leading to dimerization and clustering of alpha 4 integrins on the cell membrane and subsequent activation of the FAK-RhoA pathway. Abolishment of Hsp90-alpha 4 interaction inhibited fever-induced T cell trafficking to draining lymph nodes and impaired the clearance of bacterial infection. Our findings identify the Hsp90-alpha 4-]integrin axis as a thermal sensory pathway that promotes T lymphocyte trafficking and enhances immune surveillance during infection.