Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and ?4 Integrins.

ABSTRACT: 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 ?4 integrin activation and signaling in T cells. By inducing selective binding of Hsp90 to ?4 integrins, but not ?2 integrins, fever increased ?4-integrin-mediated T cell adhesion and transmigration. Mechanistically, Hsp90 bound to the ?4 tail and activated ?4 integrins via inside-out signaling. Moreover, the N and C termini of one Hsp90 molecule simultaneously bound to two ?4 tails, leading to dimerization and clustering of ?4 integrins on the cell membrane and subsequent activation of the FAK-RhoA pathway. Abolishment of Hsp90-?4 interaction inhibited fever-induced T cell trafficking to draining lymph nodes and impaired the clearance of bacterial infection. Our findings identify the Hsp90-?4-integrin axis as a thermal sensory pathway that promotes T lymphocyte trafficking and enhances immune surveillance during infection.

SUBMITTER: Lin C 

PROVIDER: S-EPMC6432644 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature