Previous studies have shown that
IL-22, one of the Th17 cell-related
cytokines, plays multiple roles in regulating allergic airway
inflammation caused by
antigen-specific Th2 cells; however, the underlying mechanism remains unclear. Here, we show that allergic airway
inflammation and Th2 and Th17
cytokine production upon intratracheal administration of house dust mite (HDM) extract, a representative
allergen, were exacerbated in IL-22-deficient mice. We also found that
IL-22 induces Reg3γ production from lung epithelial cells through STAT3 activation and that neutralization of Reg3γ significantly exacerbates HDM-induced eosinophilic airway
inflammation and Th2
cytokine induction. Moreover, exostatin-like 3 (EXTL3), a functional Reg3γ
binding protein, is expressed in lung epithelial cells, and intratracheal administration of recombinant Reg3γ suppresses HDM-induced
thymic stromal lymphopoietin and
IL-33 expression and accumulation of type 2 innate lymphoid cells in the lung. Collectively, these results suggest that
IL-22 induces Reg3γ production from lung epithelial cells and inhibits the development of HDM-induced allergic airway
inflammation, possibly by inhibiting
cytokine production from lung epithelial cells.