Université de Orléans and CNRS-UMR6218, Molecular Immunology and Embryology, 3B Rue de la Férollerie, 45071 Orléans Cedex 2, France.
Am J Respir Crit Care Med. 2011 May 1;183(9):1153-63. doi: 10.1164/rccm.201008-1383OC. Epub 2011 Feb 4.
IL-22 has both proinflammatory and antiinflammatory properties. Its role in allergic lung inflammation has not been explored.
To investigate the expression and roles of IL-22 in the onset and resolution of experimental allergic asthma and its cross-talk with IL-17A.
IL-22 expression was assessed in patient samples and in the lung of mice immunized and challenged with ovalbumin. IL-22 functions in allergic airway inflammation were evaluated using mice deficient in IL-22 or anti-IL-22 neutralizing antibodies. Moreover, the effects of recombinant IL-22 and IL-17A neutralizing antibodies were investigated.
Increased pulmonary IL-22 expression is found in the serum of patients with asthma and mice immunized and challenged with ovalbumin. Allergic lung inflammation is IL-22 dependent because eosinophil recruitment, Th2 cytokine including IL-13 and IL-33, chemokine production, airway hyperreactivity, and mucus production are drastically reduced in mice deficient in IL-22 or by IL-22 antibody neutralization during immunization of wild-type mice. By contrast, IL-22 neutralization during antigen challenge enhanced allergic lung inflammation with increased Th2 cytokines. Consistent with this, recombinant IL-22 given with allergen challenge protects mice from lung inflammation. Finally, IL-22 may regulate the expression and proinflammatory properties of IL-17A in allergic lung inflammation.
IL-22 is required for the onset of allergic asthma, but functions as a negative regulator of established allergic inflammation. Our study reveals that IL-22 contributes to the proinflammatory properties of IL-17A in experimental allergic asthma.
IL-22 具有促炎和抗炎特性。其在过敏性肺炎症中的作用尚未被探索。
研究 IL-22 在实验性过敏性哮喘发病和缓解中的表达和作用及其与 IL-17A 的相互作用。
评估患者样本和卵白蛋白免疫和激发的小鼠肺中 IL-22 的表达。使用缺乏 IL-22 或抗 IL-22 中和抗体的小鼠评估 IL-22 在过敏性气道炎症中的作用。此外，还研究了重组 IL-22 和 IL-17A 中和抗体的作用。
在哮喘患者的血清和卵白蛋白免疫和激发的小鼠中发现肺 IL-22 表达增加。过敏性肺炎症依赖于 IL-22，因为缺乏 IL-22 的小鼠或在野生型小鼠免疫过程中用 IL-22 抗体中和时，嗜酸性粒细胞募集、Th2 细胞因子（包括 IL-13 和 IL-33）、趋化因子产生、气道高反应性和粘液产生均显著减少。相比之下，在抗原挑战期间中和 IL-22 会增强过敏性肺炎症，增加 Th2 细胞因子。与此一致，在用过敏原激发时给予重组 IL-22 可保护小鼠免受肺炎症。最后，IL-22 可能调节过敏性肺炎症中 IL-17A 的表达和促炎特性。
IL-22 是过敏性哮喘发病所必需的，但作为已建立的过敏性炎症的负调节剂发挥作用。我们的研究表明，IL-22 有助于实验性过敏性哮喘中 IL-17A 的促炎特性。
