Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan.
J Allergy Clin Immunol. 2011 Nov;128(5):1067-76.e1-6. doi: 10.1016/j.jaci.2011.06.018. Epub 2011 Jul 26.
IL-22 functions as both a proinflammatory cytokine and an anti-inflammatory cytokine in various inflammations, depending on the cellular and cytokine milieu. However, the roles of IL-22 in the regulation of allergic airway inflammation are still largely unknown.
We sought to determine whether IL-22 is involved in the regulation of allergic airway inflammation.
We examined IL-22 production and its cellular source at the site of antigen-induced airway inflammation in mice. We also examined the effect of IL-22 neutralization, as well as IL-22 administration, on antigen-induced airway inflammation. We finally examined the effect of IL-22 on IL-25 production from a lung epithelial cell line (MLE-15 cells).
Antigen inhalation induced IL-22 production in the airways of sensitized mice. CD4(+) T cells, but not other lymphocytes or innate cells, infiltrating in the airways produced IL-22, and one third of IL-22-producing CD4(+) T cells also produced IL-17A. The neutralization of IL-22 by anti-IL-22 antibody enhanced antigen-induced IL-13 production, eosinophil recruitment, and goblet cell hyperplasia in the airways. On the other hand, intranasal administration of recombinant IL-22 attenuated antigen-induced eosinophil recruitment into the airways. Moreover, anti-IL-22 antibody enhanced antigen-induced IL-25 production in the airways, and anti-IL-25 antibody reversed the enhancing effect of anti-IL-22 antibody on antigen-induced eosinophil recruitment into the airways. Finally, IL-22 inhibited IL-13-mediated enhancement of IL-25 expression in IL-1β- or LPS-stimulated MLE-15 cells.
IL-22 attenuates antigen-induced airway inflammation, possibly by inhibiting IL-25 production by lung epithelial cells.
IL-22 在各种炎症中既可以作为促炎细胞因子，也可以作为抗炎细胞因子，这取决于细胞和细胞因子的环境。然而，IL-22 在调节过敏性气道炎症中的作用在很大程度上仍不清楚。
我们旨在确定 IL-22 是否参与调节过敏性气道炎症。
我们检测了抗原诱导的气道炎症部位中 IL-22 的产生及其细胞来源。我们还研究了 IL-22 中和以及 IL-22 给药对抗原诱导的气道炎症的影响。最后，我们检测了 IL-22 对肺上皮细胞系（MLE-15 细胞）中 IL-25 产生的影响。
抗原吸入诱导了致敏小鼠气道中 IL-22 的产生。浸润气道的 CD4+T 细胞，而不是其他淋巴细胞或固有细胞，产生了 IL-22，三分之一的产生 IL-22 的 CD4+T 细胞也产生了 IL-17A。抗 IL-22 抗体中和 IL-22 增强了抗原诱导的气道中 IL-13 的产生、嗜酸性粒细胞募集和杯状细胞增生。另一方面，鼻内给予重组 IL-22 减弱了抗原诱导的嗜酸性粒细胞向气道的募集。此外，抗 IL-22 抗体增强了抗原诱导的气道中 IL-25 的产生，抗 IL-25 抗体逆转了抗 IL-22 抗体对抗原诱导的气道中嗜酸性粒细胞募集的增强作用。最后，IL-22 抑制了 IL-13 介导的 IL-1β 或 LPS 刺激的 MLE-15 细胞中 IL-25 表达的增强。
IL-22 减弱了抗原诱导的气道炎症，可能是通过抑制肺上皮细胞中 IL-25 的产生。
