Gain of Function of Ion Channel TRPV1 Exacerbates Experimental Colitis by Promoting Dendritic Cell Activation.
Gain of Function of Ion Channel TRPV1 Exacerbates Experimental Colitis by Promoting Dendritic Cell Activation.
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DOI：
10.1016/j.omtn.2020.10.006
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发表时间：
2020-12-04
期刊：
影响因子：
--
通讯作者：
Dai Y
中科院分区：
文献类型：
--
作者：
Duo L;Wu T;Ke Z;Hu L;Wang C;Teng G;Zhang W;Wang W;Ge Q;Yang Y;Dai Y
粘膜免疫失调在炎症性肠病（IBD）的病理生理学中起着重要作用。瞬时受体电位香草素1（TRPV 1）是一种Ca 2+渗透性离子通道，参与调节免疫反应。然而，其在肠道炎症发病机制中的作用仍然是难以捉摸的。在这里，我们发现TRPV 1功能的获得显著增加了小鼠对实验性结肠炎的易感性，并且与树突状细胞的过度募集和结肠固有层中Th 17免疫应答的增强有关。TRPV 1功能的获得促进了树突状细胞的活化和炎症刺激后细胞因子的产生，从而增强了树突状细胞介导的Th 17细胞分化。进一步的机制研究表明，TRPV 1在树突状细胞中的功能获得增强了由炎症刺激诱导的钙调神经磷酸酶/活化T细胞核因子（NFATc 2）信号传导的活化。此外，在IBD患者中，与健康对照组相比，TRPV 1表达在炎症结肠的固有层细胞中增加。我们的研究结果确定了TRPV 1在调节树突状细胞活化和维持Th 17对炎症刺激的反应中的重要作用，这表明TRPV 1可能是控制粘膜免疫和IBD的潜在治疗靶点。瞬时受体电位香草酸1（TRPV 1）是一种钙离子渗透性离子通道，通常被认为是神经元中的伤害性受体。通过使用一种新的小鼠模型，作者表明TRPV 1功能的获得增强了树突状细胞在炎症刺激下的活化，从而维持了Th 17细胞分化和结肠炎反应。
Dysregulated mucosal immunity plays an essential role in the pathophysiology of inflammatory bowel disease (IBD). Transient receptor potential vanilloid 1 (TRPV1) is a Ca2+-permeable ion channel that is implicated in modulating immune responses. However, its role in the pathogenesis of intestinal inflammation remains elusive. Here, we found that TRPV1 gain of function significantly increased the susceptibility of mice to experimental colitis, and that was associated with excessive recruitment of dendritic cells and enhanced Th17 immune responses in the lamina propria of colon. TRPV1 gain of function promoted dendritic cell activation and cytokine production upon inflammatory stimuli, and consequently enhanced dendritic cell-mediated Th17 cell differentiation. Further mechanistic studies showed that TRPV1 gain of function in dendritic cells enhanced activation of calcineurin/nuclear factor of activated T cells (NFATc2) signaling induced by inflammatory stimuli. Moreover, in patients with IBD, TRPV1 expression was increased in lamina propria cells of inflamed colon compared with healthy controls. Our findings identify an important role for TRPV1 in modulating dendritic cell activation and sustaining Th17 responses to inflammatory stimuli, which suggest that TRPV1 might be a potential therapeutic target in controlling mucosal immunity and IBD. Transient receptor potential vanilloid 1 (TRPV1) is a Ca2+-permeable ion channel mostly known as a nociceptive receptor in neurons. By using a novel murine model, the authors showed that TRPV1 gain of function enhances dendritic cell activation upon inflammatory stimuli, and consequently sustains Th17 cell differentiation and colitogenic responses.
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期刊：
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影响因子：
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通讯作者：
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10.1073/pnas.0407780102
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Basu, S;Srivastava, P
通讯作者：
Srivastava, P