ZAUM-Center of Allergy and Environment, Technische Universität and Helmholtz Center Munich, Munich, Germany.
J Allergy Clin Immunol. 2013 Feb;131(2):562-70. doi: 10.1016/j.jaci.2012.09.036. Epub 2012 Nov 19.
IL-22 controls tissue homeostasis by both proinflammatory and anti-inflammatory effects. However, the anti-inflammatory mechanisms of IL-22 remain poorly investigated.
We sought to investigate the anti-inflammatory role for IL-22 in human asthma.
T-cell lines derived from lung biopsy specimens of asthmatic patients were characterized by means of flow cytometry. Human bronchial epithelial cells from healthy and asthmatic subjects were stimulated with IL-22, IFN-γ, or the combination of both cytokines. Effects of cytokine stimulation were investigated by using whole-genome analysis, ELISA, and flow cytometry. The functional consequence of cytokine stimulation was evaluated in an in vitro wound repair model and T cell-mediated cytotoxicity experiments. In vivo cytokine expression was measured by using immunohistochemistry and Luminex assays in bronchoalveolar lavage fluid of healthy and asthmatic patients.
The current study identifies a tissue-restricted antagonistic interplay of IL-22 and the proinflammatory cytokine IFN-γ. On the one hand, IFN-γ antagonized IL-22-mediated induction of the antimicrobial peptide S100A7 and epithelial cell migration in bronchial epithelial cells. On the other hand, IL-22 decreased epithelial susceptibility to T cell-mediated cytotoxicity by inhibiting the IFN-γ-induced expression of MHC-I, MHC-II, and CD54/intercellular adhesion molecule 1 molecules. Likewise, IL-22 inhibited IFN-γ-induced secretion of the proinflammatory chemokines CCL5/RANTES and CXCL10/interferon-inducible protein 10 in vitro. Consistently, the IL-22 expression in bronchoalveolar lavage fluid of asthmatic patients inversely correlated with the expression of CCL5/RANTES and CXCL10/interferon-inducible protein 10 in vivo.
IL-22 might control the extent of IFN-γ-mediated lung inflammation and therefore play a tissue-restricted regulatory role.
IL-22 通过促炎和抗炎作用来控制组织稳态。然而，IL-22 的抗炎机制仍未得到充分研究。
我们旨在研究 IL-22 在人类哮喘中的抗炎作用。
通过流式细胞术对来自哮喘患者肺活检标本的 T 细胞系进行了特征描述。用 IL-22、IFN-γ 或这两种细胞因子的组合刺激健康和哮喘患者的人支气管上皮细胞。通过全基因组分析、ELISA 和流式细胞术研究细胞因子刺激的效果。在体外伤口修复模型和 T 细胞介导的细胞毒性实验中评估细胞因子刺激的功能后果。通过免疫组织化学和 Luminex 测定法在健康和哮喘患者的支气管肺泡灌洗液中测量体内细胞因子表达。
本研究确定了 IL-22 和促炎细胞因子 IFN-γ 之间的组织特异性拮抗相互作用。一方面，IFN-γ 拮抗了 IL-22 介导的支气管上皮细胞中抗菌肽 S100A7 和上皮细胞迁移的诱导。另一方面，IL-22 通过抑制 IFN-γ 诱导的 MHC-I、MHC-II 和 CD54/细胞间黏附分子 1 分子的表达，降低了上皮细胞对 T 细胞介导的细胞毒性的敏感性。同样，IL-22 抑制了 IFN-γ 诱导的体外促炎趋化因子 CCL5/RANTES 和 CXCL10/干扰素诱导蛋白 10 的分泌。一致地，哮喘患者支气管肺泡灌洗液中的 IL-22 表达与体内 CCL5/RANTES 和 CXCL10/干扰素诱导蛋白 10 的表达呈负相关。
IL-22 可能控制 IFN-γ 介导的肺部炎症的程度，因此发挥组织特异性的调节作用。
