Forced expression of murine IL-17E induces growth retardation, jaundice, a Th2-biased response, and multiorgan inflammation in mice
Forced expression of murine IL-17E induces growth retardation, jaundice, a Th2-biased response, and multiorgan inflammation in mice
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DOI：
10.4049/jimmunol.167.11.6559
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发表时间：
2001-12-01
影响因子：
4.4
通讯作者：
Gurney, AL
中科院分区：
文献类型：
--
作者：
Pan, GH;French, D;Gurney, AL
IL-17是一种促炎细胞因子，其体内表达可诱导小鼠中性粒细胞增多。IL-17E是新近发现的一个与IL-17相关的细胞因子家族成员。IL-17E与IL-17R亲缘关系较远的蛋白IL-17Rh1结合，提示IL-17E可能具有独特的生物学功能。在这项研究中，我们已经确定了IL-17E的小鼠同源基因，并开发了转基因小鼠来表征其在体内的作用。揭示了小鼠IL-17E过表达的生物学后果，既是IL-17E所独有的，也是与IL-17相似的。暴露于mIL-17E可导致以嗜酸性粒细胞增多为特征的偏向Th2反应，增加血清IgE和IgG1，并在许多组织中观察到Th2细胞因子谱，包括血清IL-13和IL-5水平升高以及IL-4、IL-5、IL-10和IL-13基因表达升高。几种组织中干扰素-γ的基因表达增加，血清肿瘤坏死因子-α水平升高。此外，IL-17E在体外诱导G-CSF的产生，mIL-17E转基因小鼠血清G-CSF升高，并表现出中性粒细胞增多，这是IL-17所共有的特性。此外，暴露于mIL-17E可引起多种组织的病理改变，特别是肝、心和肺，其特征是混合性炎症细胞浸润、上皮细胞增生和肥大。综上所述，这些发现提示IL-17E是一种独特的多效性细胞因子，可能是炎症和免疫反应的重要介质。
IL-17 is a proinflammatory cytokine, and its in vivo expression induces neutrophilia in mice. IL-17E is a recently described member of an emerging family of IL-17-related cytokines. IL-17E has been shown to bind IL-17Rh1, a protein distantly related to the IL-17R, suggesting that IL-17E probably possesses unique biological functions. In this study,we have identified the murine ortholog of IL-17E and developed transgenic mice to characterize its actions in vivo. Biological consequences of overexpression of murine (m)IL-17E, both unique to IL-17E and similar to IL-17, were revealed. Exposure to mIL-17E resulted in a Th2-biased response, characterized by eosinophilia, increased serum IgE and IgG1, and a Th2 cytokine profile including elevated serum levels of IL-13 and IL-5 and elevated gene expression of IL-4, IL-5, IL-10, and IL-13 was observed in many tissues. Increased gene expression of IFN-gamma in several tissues and elevated serum TNF-alpha were also noted. In addition, IL-17E induces G-CSF production in vitro and mIL-17E-transgenic mice had increased serum G-CSF and exhibit neutrophilia, a property shared by IL-17. Moreover, exposure to mIL-17E elicited pathological changes in multiple tissues, particularly liver, heart, and lungs, characterized by mixed inflammatory cell infiltration, epithelial hyperplasia, and hypertrophy. Taken together, these findings suggest that IL-17E is a unique pleiotropic cytokine and may be an important mediator of inflammatory and immune responses.