Development of proteoglycan-induced arthritis is independent of IL-17.
Development of proteoglycan-induced arthritis is independent of IL-17.
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DOI：
10.4049/jimmunol.181.1.329
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发表时间：
2008-07-01
影响因子：
4.4
通讯作者：
Finnegan, Alison
中科院分区：
文献类型：
--
作者：
Doodes, Paul D.;Cao, Yanxia;Hamel, Keith M.;Wang, Yumei;Farkas, Balint;Iwakura, Yoichiro;Finnegan, Alison
IL-17是新发现的辅助性T细胞亚群Th17的标志性细胞因子。在多种自身免疫性疾病模型中，Th17细胞是炎症的重要促发因子；特别是胶原诱导的关节炎（CIA）和实验性自身免疫性脑脊髓炎（EAE），这两种疾病以前被定性为th1介导的疾病。尽管CIA和EAE分泌高水平的IFN-γ，但由于IFN-γ抑制IL-17分泌的能力，IFN-γ或IFN-γ受体缺陷小鼠的疾病加重。然而，在蛋白多糖诱导的关节炎（PGIA）中，严重的关节炎依赖于IFN-γ的产生。因此，我们对确定IL-17在PGIA中的作用感兴趣。我们评估了IL-17缺陷（IL-17−/−）小鼠关节炎的进展，发现野生型（WT）和IL-17−/−小鼠关节炎的发病和严重程度相当。尽管有证据表明IL-17参与中性粒细胞募集，但在WT和IL-17 - / -小鼠中，关节炎关节滑液中Gr1+中性粒细胞的比例相当。IL-17也与自身免疫性关节炎的骨破坏有关，然而，对WT和IL-17−/−小鼠关节炎关节的组织学分析显示，尽管RANKL表达显著降低，但关节细胞、软骨破坏和骨侵蚀的程度相似。WT和IL-17−/−在促炎细胞因子表达、T细胞增殖和自身抗体产生方面仅存在细微差异。这些数据表明，自身免疫性关节炎并不绝对需要IL-17，其他促炎介质的产生足以弥补PGIA中IL-17的损失。
IL-17 is the hallmark cytokine for the newly identified subset of T helper cells, Th17. Th17 cells are important instigators of inflammation in several models of autoimmune disease; in particular, collagen induced arthritis (CIA) and experimental autoimmune encephalomyelitis (EAE), which were previously characterized as Th1-mediated diseases. Although high levels of IFN-γ are secreted in CIA and EAE, disease is exacerbated in IFN-γ or IFN-γ receptor deficient mice due to the ability of IFN-γ to suppress IL-17 secretion. However, in proteoglycan-induced arthritis (PGIA), severe arthritis is dependent on the production of IFN-γ. We were therefore interested in determining the role of IL-17 in PGIA. We assessed the progression of arthritis in IL-17-deficient (IL-17−/−) mice and found the onset and severity of arthritis equivalent in wildtype (WT) and IL-17−/− mice. Despite evidence that IL-17 is involved in neutrophil recruitment, synovial fluid from arthritic joints showed a comparable proportion of Gr1+ neutrophils in WT and IL-17−/− mice. IL-17 is also implicated in bone destruction in autoimmune arthritis, however histological analysis of the arthritic joints from WT and IL-17−/− mice revealed a similar extent of joint cellularity, cartilage destruction and bone erosion despite significantly reduced RANKL expression. There were only subtle differences between WT and IL-17−/− in pro-inflammatory cytokine expression, T cell proliferation and autoanibody production. These data demonstrate that IL-17 is not absolutely required for autoimmune arthritis and production of other proinflammatory mediators are sufficient to compensate for the loss of IL-17 in PGIA.
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影响因子：
4.4
作者：
Finnegan, A;Grusby, MJ;Zhang, J
通讯作者：
Zhang, J
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
4.4
作者：
Cruz, Andrea;Khader, Shabaana A.;Castro, Antonio G.
通讯作者：
Castro, Antonio G.
影响因子：
4.3
作者：
Hofstetter, HH;Ibrahim, SM;Gold, R
通讯作者：
Gold, R
影响因子：
56.9
作者：
Hwang, ES;Szabo, SJ;Glimcher, LH
通讯作者：
Glimcher, LH