UC San Diego

Chronic viral infections afflict hundreds of millions of people worldwide, representing a huge financial and health burden. The interleukin-6 family cytokines are potent immune modulators, which signal through a common gp130 co-receptor. IL-27, a novel member of the IL-6 family, is a pleotropic cytokine with both activating and immunosuppressing roles in antiviral immunity. Previous research from our lab showed immune response defects to LCMV viral infection in IL27R-/- mice including decreased type-I interferon, reduced antibody production, and loss of viral control. To assess the temporal and therapeutic importance of IL-27, I treated mice with IL-27 or blocked its receptor and monitored host responses to chronic LCMV infection. Neither IL-27 administration nor IL-27R blockade altered the immune responses to LCMV. In contrast, studies with IL27R-/-IL6R-/- mice recapitulated the IL27R-/- immune defects. Comparisons between IL27R-/-IL6R-/- mice, and previously published L6R-/- mice and IL27R-/- mice showed regulation of several immune responses against LCMV to be under control of Interleukin-27 including T cell accumulation, viral specific T cell maintenance and IgG production. Taken together, our work demonstrates an important role for IL-27 in viral control.