IL-22在室内尘螨诱导模型中促进Reg3γ表达抑制过敏性炎症反应
2017/09/29
摘要
以往研究表明，作为th17细胞相关的细胞因子，IL-22在抗原特异性th2细胞引起的气道变应性炎症中发挥多种调控作用，但其作用机制目前尚不清楚。室内尘螨提取物（HdM）是一种代表性的过敏原，本实验中，IL-22表达缺陷小鼠气道给予HdM刺激后，气道变应性炎症加重，th2及th17细胞因子表达增加。我们还发现，IL-22可通过激活StAt3信号通路促进Reg3γ在肺上皮细胞中的表达，而降低Reg3γ表达后HdM诱导的嗜酸粒细胞性气道炎症及th2细胞因子表达显著增强。此外，reg3γ结合蛋白EXtL3表达于肺上皮细胞中，小鼠气道中给予重组reg3γ刺激后抑制了胸腺基质淋巴细胞生成素及IL-33的表达，促进肺脏中2型先天性淋巴样细胞聚集。综上表明，IL-22可能是通过抑制细胞因子表达，进而促进肺上皮细胞中reg3γ表达及抑制HdM诱导的气道变应性炎症。
IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite–induced asthma models.
Takashi Ito, Koichi Hirose, Aiko Saku, Kenta Kono, Hiroaki Takatori, Tomohiro Tamachi,Yoshiyuki Goto, Jean-Christophe Renauld, Hiroshi Kiyono, and Hiroshi Nakajima.
Abstract
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-specifc 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-defcient mice. We also found that IL-22 induces reg3γ production from lung epithelial cells through StAt3 activation and that neutralization of reg3γ signifcantly 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.
以往研究表明，作为th17细胞相关的细胞因子，IL-22在抗原特异性th2细胞引起的气道变应性炎症中发挥多种调控作用，但其作用机制目前尚不清楚。室内尘螨提取物（HdM）是一种代表性的过敏原，本实验中，IL-22表达缺陷小鼠气道给予HdM刺激后，气道变应性炎症加重，th2及th17细胞因子表达增加。我们还发现，IL-22可通过激活StAt3信号通路促进Reg3γ在肺上皮细胞中的表达，而降低Reg3γ表达后HdM诱导的嗜酸粒细胞性气道炎症及th2细胞因子表达显著增强。此外，reg3γ结合蛋白EXtL3表达于肺上皮细胞中，小鼠气道中给予重组reg3γ刺激后抑制了胸腺基质淋巴细胞生成素及IL-33的表达，促进肺脏中2型先天性淋巴样细胞聚集。综上表明，IL-22可能是通过抑制细胞因子表达，进而促进肺上皮细胞中reg3γ表达及抑制HdM诱导的气道变应性炎症。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(1. J Exp Med. 2017 Aug 15. pii: jem.20162108. doi: 10.1084/jem.20162108. [Epub ahead of print])
(1. J Exp Med. 2017 Aug 15. pii: jem.20162108. doi: 10.1084/jem.20162108. [Epub ahead of print])
IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite–induced asthma models.
Takashi Ito, Koichi Hirose, Aiko Saku, Kenta Kono, Hiroaki Takatori, Tomohiro Tamachi,Yoshiyuki Goto, Jean-Christophe Renauld, Hiroshi Kiyono, and Hiroshi Nakajima.
Abstract
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-specifc 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-defcient mice. We also found that IL-22 induces reg3γ production from lung epithelial cells through StAt3 activation and that neutralization of reg3γ signifcantly 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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β2肾上腺受体激动剂通过不典型的c-AMP参与的信号通路激活细胞内钙离子
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