Summary: Researchers shed light on how a fever helps our immune systems fight infection. The study reports high temperature alters surface proteins of lymphocytes, making it easier for them to travel through blood vessels to reach infection sites.
Chen and colleagues discovered that fever increases the expression of heat shock protein 90 (Hsp 90) in T lymphocytes. This protein binds to a type of integrin on the lymphocytes — α4 integrins — which promote lymphocyte adhesion to the blood vessel and ultimately to expedited migration to the site of infection.
The researchers learned that fever-induced Hsp90 binds to the integrin tail and induces integrin activation. NeuroscienceNews.com image is in the public domain.
Original Research: Open access research for “Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and α4 Integrins” by ChangDong Lin et al in Immunity. Published January 16 2019.
Cell Press”Fever Alters Immune Cells So They Can Better Reach Infections.” NeuroscienceNews. NeuroscienceNews, 16 January 2019.
Cell Press”Fever Alters Immune Cells So They Can Better Reach Infections.” http://neurosciencenews.com/fever-immune-cells-10563/ (accessed January 16, 2019).
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.