IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite-induced asthma models.
(2017) The Journal of Experimental Medicine — Vol. 214, p. 3037-3050 (2017)
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- 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.
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Ito, T., Hirose, K., Saku, A., Kono, K., Takatori, H., Tamachi, T., Goto, Y., Renauld, J.-C., Kiyono, H., & Nakajima, H. (2017). IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite-induced asthma models. The Journal of Experimental Medicine, 214, 3037-3050. https://doi.org/10.1084/jem.20162108 (Original work published 2017)