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.

先前的研究表明，IL-22是Th17细胞相关的细胞因子之一，在调节抗原特异性Th2细胞引起的过敏性气道炎症中起多种作用。但是，其潜在机制仍不清楚。在这里，我们显示在气管内施用屋尘螨（HDM）提取物（一种代表性的过敏原）后，在IL-22缺陷型小鼠中，过敏性气道炎症以及Th2和Th17细胞因子的产生加剧了。我们还发现IL-22通过STAT3激活诱导肺上皮细胞产生Reg3γ，而Reg3γ的中和作用则显着加剧了HDM诱导的嗜酸性气道炎症和Th2细胞因子的诱导。此外，功能性Reg3γ结合蛋白exostatin-like 3（EXTL3）在肺上皮细胞中表达，气管内施用重组Reg3γ可抑制HDM诱导的胸腺基质淋巴细胞生成素和IL-33的表达以及肺中2型先天性淋巴样细胞的蓄积。总的来说，这些结果表明IL-22可能通过抑制肺上皮细胞产生细胞因子来诱导肺上皮细胞产生Reg3γ，并抑制HDM诱导的过敏性气道炎症的发展。