IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite-induced asthma models.
Takashi ItoKoichi HiroseAiko SakuKenta KonoHiroaki TakatoriTomohiro TamachiYoshiyuki GotoJean-Christophe RenauldHiroshi KiyonoHiroshi NakajimaPublished in: The Journal of experimental medicine (2017)
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.
Keyphrases
- oxidative stress
- diabetic rats
- induced apoptosis
- allergic rhinitis
- high glucose
- binding protein
- drug induced
- cell cycle arrest
- bone marrow
- chronic obstructive pulmonary disease
- poor prognosis
- mesenchymal stem cells
- stem cells
- endothelial cells
- human health
- health risk
- atopic dermatitis
- risk assessment
- cell therapy
- endoplasmic reticulum stress
- cell death