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卵泡抑素样蛋白 1 通过调节基质细胞中的 IL-17RC 来调节 IL-17 信号通路。

Follistatin-like protein 1 modulates IL-17 signaling via IL-17RC regulation in stromal cells.

机构信息

Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.

出版信息

Immunol Cell Biol. 2017 Sep;95(8):656-665. doi: 10.1038/icb.2017.26. Epub 2017 Apr 5.

DOI:10.1038/icb.2017.26
PMID:28377613
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5609702/
Abstract

Follistatin-like protein 1 (FSTL-1) possesses several newly identified roles in mammalian biology, including interleukin (IL)-17-driven inflammation, though the mechanism underlying FSTL-1 influence on IL-17-mediated cytokine production is unknown. Using parallel in vitro bone marrow stromal cell models of FSTL-1 suppression, we employed unbiased microarray analysis to identify FSTL-1-regulated genes and pathways that could influence IL-17-dependent production of IL-6 and granulocyte colony-stimulating factor. We discovered that FSTL-1 modulates Il17rc gene expression. Specifically, FSTL-1 was necessary for Il17rc gene transcription, IL-17RC surface protein expression and IL-17-dependent cytokine production. This work identifies a mechanism by which FSTL-1 influences IL-17-driven inflammatory signaling in vitro and reveals a novel function for FSTL-1, as a modulator of gene expression. Thus enhanced understanding of the interplay between FSTL-1 and IL-17-mediated inflammation may provide insight into potential therapeutic targets of IL-17-mediated diseases and warrants ongoing study of in vivo models and clinical scenarios of FSTL-1-influenced diseases.

摘要

卵泡抑素样蛋白 1（FSTL-1）在哺乳动物生物学中具有几个新确定的作用，包括白细胞介素（IL）-17 驱动的炎症，尽管 FSTL-1 对 IL-17 介导的细胞因子产生影响的机制尚不清楚。使用 FSTL-1 抑制的体外平行骨髓基质细胞模型，我们采用无偏倚微阵列分析来鉴定 FSTL-1 调节的基因和通路，这些基因和通路可能影响 IL-17 依赖性 IL-6 和粒细胞集落刺激因子的产生。我们发现 FSTL-1 调节 Il17rc 基因的表达。具体而言，FSTL-1 是 Il17rc 基因转录、IL-17RC 表面蛋白表达和 IL-17 依赖性细胞因子产生所必需的。这项工作确定了 FSTL-1 在体外影响 IL-17 驱动的炎症信号的机制，并揭示了 FSTL-1 的新功能，即作为基因表达的调节剂。因此，深入了解 FSTL-1 与 IL-17 介导的炎症之间的相互作用可能为 IL-17 介导的疾病的潜在治疗靶点提供深入的了解，并需要对体内模型和 FSTL-1 影响疾病的临床情况进行持续研究。

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