Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor
Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor
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DOI：
10.1182/blood-2006-10-052787
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发表时间：
2007-04-15
期刊：
影响因子：
20.3
通讯作者：
O'Connell, Peta J.
中科院分区：
文献类型：
--
作者：
Leon-Ponte, Matilde;Ahern, Gerard P.;O'Connell, Peta J.
尽管通常被认为是一种神经递质，但有大量证据表明，血清素 (5-HT) 在炎症性疾病的发病机制中发挥着重要作用。尽管有这些发现，5-HT 在调节免疫功能（特别是 T 细胞功能）中的确切作用仍然难以捉摸。我们报告说，初始 T 细胞主要表达 7 型 5-HT 受体 (5-HTR)，并且该蛋白的表达在 T 细胞激活时显着增强。此外，T 细胞激活会导致 5-HT1B 和 5-HT2A 受体的表达。值得注意的是，外源 5-HT 会诱导初始 T 细胞中细胞外信号调节激酶 1 和 -2 (ERK1/2) 以及 I kappa B α 的快速磷酸化。 5-HT 诱导的 ERK1/2 和 NF kappa B 激活可通过与特定 5-HT7 受体拮抗剂预孵育来抑制。因此，通过 5-HT7 受体的 5-HT 信号传导可能有助于早期 T 细胞激活。反过来，T 细胞合成的 5-HT 可能充当自分泌因子。与这一假设一致，我们发现用对氯苯丙氨酸 (PCPA) 抑制 5-HT 合成会损害 T 细胞活化和增殖。综合起来，这些数据证明了 5-HT 作为 T 细胞激活和功能的内在辅助因子的基本作用，并提出了一种替代机制，通过该机制可以通过吲哚胺 2,3-双加氧酶介导的色氨酸分解代谢来调节免疫功能。
Although typically considered a neurotransmitter, there is substantial evidence that serotonin (5-HT) plays an important role in the pathogenesis of inflammatory disorders. Despite these findings, the precise role of 5-HT in modulating immune function, particularly T-cell function, remains elusive. We report that naive T cells predominantly express the type 7 5-HT receptor (5-HTR), and expression of this protein is substantially enhanced on T-cell activation. In addition, T-cell activation leads to expression of the 5-HT1B and 5-HT2A receptors. Significantly, exogenous 5-HT induces rapid phosphorylation of extracellular signal-regulated kinase-1 and -2 (ERK1/2) and I kappa B alpha in naive T cells. 5-HT-induced activation of ERK1/2 and NF kappa B is inhibited by preincubation with a specific 5-HT7 receptor antagonist. Thus, 5-HT signaling via the 5-HT7 receptor may contribute to early T-cell activation. In turn, 5-HT synthesized by T cells may act as an autocrine factor. Consistent with this hypothesis, we found that inhibition of 5-HT synthesis with parachlorophenyl-alanine (PCPA) impairs T-cell activation and proliferation. Combined, these data demonstrate a fundamental role for 5-HT as an intrinsic cofactor in T-cell activation and function and suggest an alternative mechanism through which immune function may be regulated by indoleamine 2,3-dioxygenase-mediated catabolism of tryptophan.