The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4⁺ T cells.
The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4⁺ T cells.
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DOI：
10.1038/ni.3009
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发表时间：
2014-11
影响因子：
30.5
通讯作者：
Raz E
中科院分区：
文献类型：
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作者：
Bertin S;Aoki-Nonaka Y;de Jong PR;Nohara LL;Xu H;Stanwood SR;Srikanth S;Lee J;To K;Abramson L;Yu T;Han T;Touma R;Li X;González-Navajas JM;Herdman S;Corr M;Fu G;Dong H;Gwack Y;Franco A;Jefferies WA;Raz E
TRPV 1是一种Ca 2+渗透性通道，主要作为感觉神经元中的疼痛受体进行研究。然而，它在其他细胞类型中的作用知之甚少。在这里，我们证明了TRPV 1在CD 4 + T细胞中功能性表达，它作为一个非储存操作的Ca 2+通道，并有助于T细胞受体（TCR）诱导的Ca 2+内流，TCR信号和T细胞活化。在T细胞介导的结肠炎模型中，TRPV 1促进致结肠炎性T细胞应答和肠道炎症。此外，人类CD 4 + T细胞中TRPV 1的遗传和药理学抑制重现了鼠Trpv 1 −/− CD 4 + T细胞的表型。这些发现表明，TRPV 1抑制可能代表一种新的治疗策略，以抑制促炎性T细胞反应。
TRPV1 is a Ca2+-permeable channel mostly studied as a pain receptor in sensory neurons. However, its role in other cell types is poorly understood. Here, we demonstrate that TRPV1 is functionally expressed in CD4+ T cells where it acts as a non-store-operated Ca2+ channel and contributes to T cell receptor (TCR)-induced Ca2+ influx, TCR signaling and T cell activation. In models of T cell-mediated colitis, TRPV1 promotes colitogenic T cell responses and intestinal inflammation. Furthermore, genetic and pharmacological inhibition of TRPV1 in human CD4+ T cells recapitulates the phenotype of murine Trpv1−/− CD4+ T cells. These findings suggest that TRPV1 inhibition could represent a new therapeutic strategy to restrain proinflammatory T cell responses.