Interleukin-17A promotes CD8⁺ T cell cytotoxicity to facilitate West Nile virus clearance

CD8⁺ T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8⁺ T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a^-/-) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8⁺ T cells isolated from Il17a^-/- mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in vivo. Importantly, treatment of WNV-infected mice with recombinant IL- 17A, as late as day 6 postinfection, significantly reduces the viral burden and increases survival, suggesting a therapeutic potential for IL-17A. In conclusion, we report a novel function of IL-17A in promoting CD8⁺ T cell cytotoxicity, which may have broad implications in other microbial infections and cancers.