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

Background IL-22 functions as both a proinflammatory cytokine and an anti-inflammatory cytokine in various inflammations, depending on the cellular and cytokine milieu. However, the roles of IL-22 in the regulation of 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, on antigen-induced airway inflammation. 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 the airways of sensitized mice. CD4+ T cells, but not other lymphocytes or innate cells, infiltrating in the airways produced IL-22, and one third of IL-22–producing CD4+ T cells also produced IL-17A. The neutralization of IL-22 by anti–IL-22 antibody enhanced antigen-induced IL-13 production, eosinophil recruitment, and goblet cell hyperplasia in the airways. On the other hand, intranasal administration of recombinant IL-22 attenuated antigen-induced eosinophil recruitment into the airways. Moreover, anti–IL-22 antibody enhanced antigen-induced IL-25 production in the airways, and anti–IL-25 antibody reversed the enhancing effect of anti–IL-22 antibody on antigen-induced 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.