IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite-induced asthma models.
IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite-induced asthma models.
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DOI：
10.1084/jem.20162108
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发表时间：
2017-10-02
期刊：
影响因子：
--
通讯作者：
Nakajima H
中科院分区：
文献类型：
--
作者：
Ito T;Hirose K;Saku A;Kono K;Takatori H;Tamachi T;Goto Y;Renauld JC;Kiyono H;Nakajima H
Ito等人表明，主要由CD 4 + T细胞产生的IL-22通过STAT 3活化诱导肺上皮细胞的Reg 3 γ表达，并通过抑制上皮细胞因子产生来抑制过敏性气道炎症。IL-22是Th 17细胞相关的细胞因子之一，在调节抗原特异性Th 2细胞引起的过敏性气道炎症中发挥多种作用，但其机制尚不清楚。在这里，我们表明，过敏性气道炎症和Th 2和Th 17细胞因子的产生后，室内给药的屋尘螨（HDM）提取物，一个代表性的过敏原，加剧了IL-22缺陷小鼠。我们还发现IL-22通过STAT 3激活诱导肺上皮细胞产生Reg 3 γ，并且Reg 3 γ的中和显著加剧了HDM诱导的嗜酸性气道炎症和Th 2细胞因子诱导。此外，外抑素样3（EXTL 3），一种功能性Reg 3 γ结合蛋白，在肺上皮细胞中表达，并且重组Reg 3 γ的腹膜内给药抑制HDM诱导的胸腺基质淋巴细胞生成素和IL-33表达以及肺中2型先天淋巴样细胞的积累。总的来说，这些结果表明IL-22诱导肺上皮细胞产生Reg 3 γ，并抑制HDM诱导的过敏性气道炎症的发展，可能是通过抑制肺上皮细胞产生细胞因子。
Ito et al. show that IL-22, which is produced mainly by CD4+ T cells, induces Reg3γ expression from lung epithelial cells through STAT3 activation and suppresses allergic airway inflammation via the inhibition of epithelial cytokine production. 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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