The interleukin-1 family member IL-33 participates in both innate and adaptive T helper-2 immune cell responses in models of lung disease. The IL-6-type cytokine Oncostatin M (OSM) elevates lung inflammation, Th2-skewed cytokines, alternatively activated (M2) macrophages, and eosinophils in C57Bl/6 mice in vivo. Since OSM induces IL-33 expression, we here test the IL-33 function in OSM-mediated lung inflammation using IL-33-/- mice. Adenoviral OSM (AdOSM) markedly induced IL-33 mRNA and protein levels in wild-type animals while IL-33 was undetectable in IL-33-/- animals. AdOSM treatment showed recruitment of neutrophils, eosinophils, and elevated inflammatory chemokines (KC, eotaxin-1, MIP1a, and MIP1b), Th2 cytokines (IL-4/IL-5), and arginase-1 (M2 macrophage marker) whereas these responses were markedly diminished in IL-33-/- mice. AdOSM-induced IL-33 was unaffected by IL-6-/- deficiency. AdOSM also induced IL-33R+ ILC2 cells in the lung, while IL-6 (AdIL-6) overexpression did not. Flow-sorted ILC2 responded in vitro to IL-33 (but not OSM or IL-6 stimulation). Matrix remodelling genes col3A1, MMP-13, and TIMP-1 were also decreased in IL-33-/- mice. In vitro, IL-33 upregulated expression of OSM in the RAW264.7 macrophage cell line and in bone marrow-derived macrophages. Taken together, IL-33 is a critical mediator of OSM-driven, Th2-skewed, and M2-like responses in mouse lung inflammation and contributes in part through activation of ILC2 cells.

中文翻译：

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IL-33 通过 IL-6 型细胞因子制瘤素 M 介导肺部炎症

白细胞介素 1 家族成员 IL-33 参与肺病模型中的先天性和适应性 T helper-2 免疫细胞反应。IL-6 型细胞因子制瘤素 M (OSM) 可在体内升高 C57Bl/6 小鼠的肺部炎症、Th2 偏态细胞因子、交替激活 (M2) 巨噬细胞和嗜酸性粒细胞。由于 OSM 诱导 IL-33 表达，我们在这里使用 IL-33-/- 小鼠测试了 IL-33 在 OSM 介导的肺部炎症中的功能。腺病毒 OSM (AdOSM) 在野生型动物中显着诱导 IL-33 mRNA 和蛋白质水平，而在 IL-33-/- 动物中检测不到 IL-33。AdOSM 治疗显示中性粒细胞、嗜酸性粒细胞和升高的炎症趋化因子（KC、eotaxin-1、MIP1a 和 MIP1b）、Th2 细胞因子（IL-4/IL-5）和精氨酸酶-1（M2 巨噬细胞标志物）的募集，而这些反应在 IL-33-/- 小鼠中显着减少。AdOSM 诱导的 IL-33 不受 IL-6-/- 缺陷的影响。AdOSM 还在肺中诱导 IL-33R+ ILC2 细胞，而 IL-6 (AdIL-6) 过表达则不会。流排序 ILC2 响应体外IL-33（但不是 OSM 或 IL-6 刺激）。IL-33-/- 小鼠的基质重塑基因 col3A1、MMP-13 和 TIMP-1 也减少。在体外，IL-33 上调 RAW264.7 巨噬细胞系和骨髓来源的巨噬细胞中 OSM 的表达。总之，IL-33 是小鼠肺部炎症中 OSM 驱动、Th2 偏态和 M2 样反应的关键介质，部分通过激活 ILC2 细胞起作用。