Cutting edge: TNF receptor-associated factor 4 restricts IL-17-mediated pathology and signaling processes.

Cutting edge: TNF receptor-associated factor 4 restricts IL-17-mediated pathology and signaling processes.
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DOI:
10.4049/jimmunol.1200470
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发表时间:
2012-07-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Li X
Li X
中科院分区:
其他
文献类型:
--
作者:
Zepp JA;Liu C;Qian W;Wu L;Gulen MF;Kang Z;Li X

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效应t细胞亚群Th17在多发性硬化症和其他自身免疫性疾病的发病机制中起着重要作用。典型的细胞因子IL-17参与IL-17R并在刺激下招募e3连接酶Act1。在这项研究中,我们研究了TRAF4在IL-17信号传导和th17介导的自身免疫性脑脊髓炎中的作用。traf4缺陷小鼠的原代细胞显示il -17激活的信号通路和趋化因子mRNA的诱导明显增强。将MOG 35-55特异性野生型Th17细胞过继转移到traf4缺陷受体小鼠中可诱导疾病早期发病。在机制上,我们发现TRAF4和TRAF6利用了Act1上相同的traf结合位点,从而允许TRAF4与TRAF6竞争与Act1的相互作用。综上所述,本研究揭示了TRAF4在限制IL-17信号传导和th17介导的疾病中的独特作用的必要性。
The effector T-cell subset, Th17, plays a significant role in the pathogenesis of multiple sclerosis as well as other autoimmune diseases. The signature cytokine, IL-17, engages the IL-17R and recruits the E3-ligase Act1 upon stimulation. In this study we examined the role of TRAF4 in IL-17 signaling and Th17-mediated autoimmune encephalomyelitis. Primary cells from TRAF4-deficient mice displayed markedly enhanced IL-17-activated signaling pathways and induction of chemokine mRNA. Adoptive transfer of MOG 35–55 specific wild-type Th17 cells into TRAF4-deficient recipient mice induced an earlier onset of disease. Mechanistically, we found that TRAF4 and TRAF6 utilized the same TRAF-binding sites on Act1, allowing the competition of TRAF4 with TRAF6 for the interaction with Act1. Taken together, this study reveals the necessity of a unique role of TRAF4 in restricting the effects of IL-17 signaling and Th17-mediated disease.
通过 TRAF3 介导的白细胞介素 17 受体信号抑制调节实验性自身免疫性脑脊髓炎
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