Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697.
Institute for Immunology, University of California, Irvine, Irvine, CA 92697; and.
J Immunol. 2018 Dec 15;201(12):3669-3676. doi: 10.4049/jimmunol.1800435. Epub 2018 Nov 21.
We have described a novel cytokine encoded by a gene called Meteorin-like (). Metrnl is a small (∼28 kDa) secreted protein expressed by activated macrophages and barrier tissues (mucosa and skin). Metrnl production by bone marrow macrophages is induced by several cytokines including TNF-α, IL-17α, IL-12, and IL-4 and inhibited by IFN-γ and TGF-β. Metrnl expression in macrophages is also induced by LPS, and its levels in circulation are associated with inflammatory responses in vivo. Furthermore, Metrnl regulates the production of several cytokines and chemokines in macrophages. We have produced a mouse, which is viable and shows normal development. However, it exhibits dysregulated cytokine production, alterations in IgG production, and is highly susceptible to LPS in a sepsis model. Furthermore, older mice develop inflammatory lesions, suggesting that Metrnl participates in the control of inflammatory responses. Taken together, these observations indicate that encodes a novel immunoregulatory cytokine associated with inflammatory responses that we have designated Meteorin-β.
我们描述了一种新型细胞因子,它由一个名为 Meteorin-like () 的基因编码。Metrnl 是一种小的(∼28 kDa)分泌蛋白,由激活的巨噬细胞和屏障组织(黏膜和皮肤)表达。几种细胞因子包括 TNF-α、IL-17α、IL-12 和 IL-4 可诱导骨髓巨噬细胞产生 Metrnl,而 IFN-γ 和 TGF-β 则抑制其产生。LPS 也可诱导巨噬细胞中 Metrnl 的表达,其在循环中的水平与体内炎症反应相关。此外,Metrnl 还可调节巨噬细胞中几种细胞因子和趋化因子的产生。我们已制备出一种 基因敲除小鼠,该小鼠具有活力且发育正常。然而,它表现出细胞因子产生失调、IgG 产生改变,并在败血症模型中对 LPS 高度敏感。此外,年老的 小鼠会出现炎症性病变,这表明 Metrnl 参与了对炎症反应的控制。综上所述,这些观察结果表明 编码一种新型免疫调节细胞因子,与我们命名为 Meteorin-β 的炎症反应相关。