Anti-inflammatory effects of interleukin-23 receptor cytokine-binding homology region rebalance T cell distribution in rodent collagen-induced arthritis.

Anti-inflammatory effects of interleukin-23 receptor cytokine-binding homology region rebalance T cell distribution in rodent collagen-induced arthritis.
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IL-23 受体细胞因子结合同源区的抗炎作用在啮齿动物胶原诱导的关节炎中重新平衡 T 细胞分布。

DOI:
10.18632/oncotarget.9309
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发表时间:
2016-05-31
期刊:
影响因子:
--
通讯作者:
Yao W
Yao W
中科院分区:
其他
文献类型:
--
作者:
Guo W;Yu D;Wang X;Luo C;Chen Y;Lei W;Wang C;Ge Y;Xue W;Tian Q;Gao X;Yao W

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IL-23是Th 17介导的自身免疫性疾病中调节Th 17细胞分化和促进炎性细胞增殖的重要细胞因子。胶原诱导的大鼠关节炎(CIA)是一种类风湿性关节炎模型,其特征是病变部位的B和T细胞,尤其是Th 17细胞产生明显的炎症自身反应。在本研究中,我们使用rhIL-23受体阻断IL-23信号通路,以探讨IL-23在CIA大鼠Th 17/Th 9/Treg细胞比例失衡中的重要性。经rhIL-23 R-CRP治疗后,CIA大鼠IL-17和IL-9分泌明显减少,FoxP 3在此过程中被激活,提示IL-23可调节Th 17/Th 9/Treg细胞的平衡。与动物模型相似,IL-23对人成纤维细胞样滑膜细胞(HFLS)也具有显著的促炎作用,与TNF-α显示出协同结果。IL-23可调节Th 17/Th 9/Treg细胞比例失衡,rhIL-23 R-IL-23可作为RA患者的潜在治疗药物。
IL-23 is an important cytokine to regulate Th17 cell differentiation and promote the proliferation of inflammatory cells in Th17-mediated autoimmune diseases. The collagen-induced arthritis (CIA) in rat is a model of rheumatoid arthritis characterized by pronounced inflammatory auto-responses from B and T cells, especially Th17 cells in lesions. In the present study, we used rhIL23R-CHR to block the IL-23 signaling pathway to probe the importance of IL-23 in misbalancing the ratio of Th17/Th9/Treg cells in CIA rats. After treatments with rhIL23R-CHR, the CIA rats showed a significant decrease of secretions of IL-17 and IL-9, whereas FoxP3 was activated in the process, indicating that IL-23 can manipulate the balance of Th17/Th9/Treg cells. Similar to the animal model, IL-23 also possessed remarkable proinflammatory effects on human fibroblast-like synoviocyte cells (HFLS), showing synergetic outcomes with TNF-α. Together, IL-23 could act as a modulator to imbalance the ratio of Th17/Th9/Treg cells, and rhIL23R-CHR could serve as a potential therapeutic agent for RA patients.
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