IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation (59.8)

Abstract

Abstract BACKGROUND: IL-22 functions as both a proinflammatory and an anti-inflammatory cytokine in various inflammations. However, the roles of IL-22 in the allergic airway inflammation are still largely unknown. OBJECTIVE: We sought to determine whether IL-22 is involved in the regulation of allergic airway inflammation. METHODS: We examined IL-22 production and its cellular source at the site of antigen-induced airway inflammation in mice. We also examined the effect of IL-22 neutralization, as well as IL-22 administration. We finally examined the effect of IL-22 on IL-25 production from a lung epithelial cell line (MLE-15 cells). RESULTS: Antigen inhalation induced IL-22 production in CD4(+) T cells. Only one third of IL-22-producing CD4(+) T cells also produced IL-17A. Anti-IL-22 antibody administration enhanced antigen-induced IL-13 production, eosinophil recruitment, and goblet cell hyperplasia in the airways. On the other hand, intranasal administration of rIL-22 attenuated eosinophil recruitment. Moreover, anti-IL-22 antibody enhanced IL-25 production in the airways, and anti-IL-25 antibody reversed the enhancing effect of anti-IL-22 antibody on eosinophil recruitment into the airways. Finally, IL-22 inhibited IL-13-mediated enhancement of IL-25 expression in IL-1β- or LPS-stimulated MLE-15 cells. CONCLUSION: IL-22 attenuates antigen-induced airway inflammation, possibly by inhibiting IL-25 production by lung epithelial cells.