Role of interferon regulatory factor 7 in serum-transfer arthritis: regulation of interferon-β production.
Role of interferon regulatory factor 7 in serum-transfer arthritis: regulation of interferon-β production.
复制标题
干扰素调节因子 7 在血清转移性关节炎中的作用：干扰素-β 产生的调节。
DOI：
10.1002/art.33454
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发表时间：
2012
影响因子：
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通讯作者：
Kimbler,TrevorB
中科院分区：
文献类型：
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作者：
Sweeney,SusanE;Corr,Maripat;Kimbler,TrevorB
目的先天免疫反应激活滑膜细胞并将炎症细胞招募到类风湿关节中。 I 型干扰素 (IFN) 在自身免疫中发挥作用，IFN 基因转录由 IFN 调节因子 (IRF) 响应先天传感器识别而激活。本研究的目的是检查 IRF-7 遗传缺陷对被动 K/BxN 血清转移关节炎模型的影响。方法在 IRF-7−/− 小鼠中诱导被动转移关节炎，并用 IFNβ 或聚 (I-C) 治疗其他组。进行了临床关节炎评分、组织学评估、显微计算机断层扫描和滑膜组织定量聚合酶链反应分析。通过酶联免疫吸附测定 (ELISA) 分析小鼠血清。结果在被动 K/BxN 血清转移模型中，与野生型 (WT) 小鼠相比，IRF-7−/− 小鼠的关节炎严重程度显着增加。此外，滑膜和血清中 IFNβ 的表达减少，可能导致关节炎增加。注射替代性 IFNβ 的 IRF-7−/− 小鼠关节炎有所减少。 Poly(I-C) 治疗可减轻 IRF-7−/− 小鼠的关节炎，恢复滑膜 IFNβ 基因表达，并增加血清 IFNβ 水平。体外研究表明，与 WT 小鼠的 FLS 相比，IRF-7−/− 小鼠的成纤维细胞样滑膜细胞 (FLS) 的聚 (I-C) 刺激导致促炎基因表达的诱导增加；然而，IFNβ表达没有显着差异。相比之下，IRF-7−/−小鼠的腹膜巨噬细胞对聚（I-C）刺激的反应显示出明显较少的 IFNβ 诱导。结论IRF-7 缺乏会加剧关节炎，而用 IFNβ 或聚（I-C）替代治疗可降低关节炎的严重程度。 IRF-7 的巨噬细胞和滑膜细胞特异性作用可能导致关节炎的增加。 IRF-7 可能通过调节巨噬细胞 IFNβ 的产生在被动转移性关节炎中发挥抗炎作用。
ObjectiveInnate immune responses activate synoviocytes and recruit inflammatory cells into the rheumatoid joint. Type I interferons (IFNs) play a role in autoimmunity, and IFN gene transcription is activated by IFN‐regulatory factors (IRFs) in response to innate sensor recognition. The purpose of this study was to examine the effect of genetic deficiency of IRF‐7 in a passive K/BxN serum–transfer model of arthritis.MethodsPassive‐transfer arthritis was induced in IRF‐7−/−mice, and additional groups were treated with IFNβ or poly(I‐C). Clinical arthritis scoring, histologic assessment, micro–computed tomography, and synovial tissue quantitative polymerase chain reaction analysis were performed. Mouse serum was analyzed by enzyme‐linked immunosorbent assay (ELISA).ResultsIn the passive K/BxN serum–transfer model, arthritis severity was significantly increased in IRF‐7−/−mice compared with wild‐type (WT) mice. In addition, expression of IFNβ in synovium and serum was decreased, potentially contributing to increased arthritis. IRF‐7−/−mice injected with replacement IFNβ had a decrease in arthritis. Poly(I‐C) treatment diminished arthritis in IRF‐7−/−mice, restored synovial IFNβ gene expression, and increased serum levels of IFNβ. In vitro studies demonstrated that poly(I‐C) stimulation of fibroblast‐like synoviocytes (FLS) from IRF‐7−/−mice resulted in increased induction of proinflammatory gene expression as compared with FLS from WT mice; however, IFNβ expression was not significantly different. In contrast, peritoneal macrophages from IRF‐7−/−mice showed significantly less induction of IFNβ in response to poly(I‐C) stimulation.ConclusionIRF‐7 deficiency exacerbates arthritis and replacement treatment with IFNβ or poly(I‐C) decreases arthritis severity. Both macrophage‐ and synoviocyte‐specific roles of IRF‐7 likely contribute to the increased arthritis. IRF‐7 might play an antiinflammatory role in passive‐transfer arthritis through regulation of macrophage IFNβ production.