CD317 促进巨噬细胞 TLR4 信号转导的作用机制研究
CD317 促进巨噬细胞 TLR4 信号转导的作用机制研究
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国家自然科学基金委员会青年科学基金项目(82001688);深圳市科技创新委员会基础研究面上项目(JCYJ20190807164001762)

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The Mechanism of CD317 in Promoting TLR4 Signaling in Macrophage
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National Natural Science Foundation of China (82001688); Shenzhen National Natural Science Foundation of China (82001688); Shenzhen Science and Technology Innovation Commission (JCYJ20190807164001762)

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    摘要:

    Toll 样受体 4 (TLR4)是一个重要的模式识别受体,在抗感染天然免疫过程中发挥重要作用。 CD317 是一个结构独特的Ⅱ型跨膜糖蛋白,兼具病毒束缚和信号调节功能,但目前尚不清楚其对 TLR4 介导的信号转导是否有调控作用。该研究利用基因敲除鼠来源的原代腹腔巨噬细胞和 THP-1 诱导的人 巨噬细胞为模型,探讨了 CD317 对 TLR4 信号转导的作用。结果显示,CD317 能够被 TLR4 激动剂脂 多糖诱导表达,并反馈性增强脂多糖介导的 NF-κB 活化及 TNF-α、IL-1β 和 IL-6 等促炎细胞因子的产 生。CD317 敲除或敲减均能够显著抑制 TLR4 介导信号活化及细胞因子的产生。进一步利用免疫共沉 淀证实 CD317 能够与 TLR4 下游的关键蛋白 MyD88、TRAF6 相结合,提示 CD317 可能是通过 MyD88- TRAF6 信号转导,增强 TLR4 介导的 NF-κB 活化。该研究不仅加深了对 CD317 在抗感染天然免疫调控 中作用的认识,也为相关疾病的治疗策略开发提供了新的靶点和理论指导。

    Abstract:

    TLR4 is an important pattern recognition receptor that plays important roles in innate immunity against infections. CD317 is a type Ⅱ transmembrane glycoprotein with unique structure that endows it viral tethering and signaling potential. However, it is not clear yet whether CD317 regulates TLR4-mediated signal transduction. Herein, we investigated the role of CD317 on TLR4 signal transduction by using primary peritoneal macrophages derived from CD317 knockout mice and THP-1-derived human macrophages, and found that the expression of CD317 could be induced by TLR4 agonist (Lipopolysaccharide), which, in a feedback loop, further enhanced the TLR4-mediated NF-κB activation and subsequent release of pro inflammatory cytokines (TNF-α, IL-1β and IL-6, etc.). CD317 knockdown or knockout markedly impaired the TLR4 signal transduction and cytokine production. By using co-immunoprecipitation, we found that CD317 could interact with both MyD88 and TRAF6, suggesting that CD317 probably enhanced the TLR- 4-mediated NF-κB activation through MyD88-TRAF6 signal transduction pathway. Conclusively, our study not only extends the understanding on the role of CD317 in innate immune regulation, but also provides new targets and theoretical guidance for the development of effective strategies for related diseases.

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引文格式
逯晓旭,邓 湉,张鹏超,章桂忠,万晓春. CD317 促进巨噬细胞 TLR4 信号转导的作用机制研究 [J].集成技术,2021,10(5):1-11

Citing format
LU Xiaoxu, DENG Tian, ZHANG Pengchao, ZHANG Guizhong, WAN Xiaochun. The Mechanism of CD317 in Promoting TLR4 Signaling in Macrophage[J]. Journal of Integration Technology,2021,10(5):1-11

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  • 在线发布日期: 2021-09-15
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