IL-17E (IL-25) and IL-17RB promote respiratory syncytial virus-induced pulmonary disease

One of the most severe pathologic responses of RSV infection is associated with overproduction of cytokines and inflammation, leading to mucus hypersecretion. This study investigated the role of IL-25 in the develop-ment of RSV-associated immunopathology. IL-25 and its receptor IL-17RB were increased following RSV in-fection, and IL-25 blockade using neutralizing antibod-ies reduced RSV-associated pathology, AHR, and type 2 cytokine production. Likewise, IL-17RB/ mice dem-onstrated a modified inflammatory response during RSV infection characterized by decreased Th2 and in-creased Th17 cytokine production. Additionally, the IL-17RB/ mice demonstrated significantly reduced in-flammation and cytokine production in a model of RSV-driven asthma exacerbation. These results indicate that IL-25 regulates the inflammatory response to RSV in-fection and that its inhibition may enable a reduction in the severity of RSV-associated pulmonary inflamma-tion, including during viral-induced asthma exacerba-tion. J. Leukoc. Biol. 95: 000–000; 2014