Endogenous IL-21 regulates pathogenic mucosal

CD4 T-cell responses during enhanced RSV disease in mice JS Dodd1, D Clark1,2, R Muir1, C Korpis1 and PJM Openshaw1 A role for interleukin-21 (IL-21) has recentlybeen found in several diseases, but contribution tomucosal defenceshasnot been described. In BALB/c mice infected with respiratory syncytial virus (RSV), IL-21 depletion had little effect in primary infection. However, depletion of mice during priming with recombinant vaccinia expressing RSV G protein (which primesRSV-specific T helper type 2 cells and causes lung eosinophilia during RSV infection) further exacerbated pathology during RSV challenge, with reduced viral clearance and impaired virus-specific serum antibody responses. This enhancement was accompanied by lymphocyte, neutrophil, and antigen-presenting cell recruitment to the lungs, with increased bronchoalveolar lavage interferon-c and IL-17 levels. Adoptive transfer of splenic CD4 Tcells from depleted mice into naive recipients replicated these effects, indicating that IL-21 mediates its effects via CD4 T cells. Endogenous IL-21, therefore, has potent and specific effects on mucosal antiviral responses, assisting viral clearance, regulating pulmonary T- and B-cell responses, and inhibiting IL-17 production