Reconciling neuronally and nonneuronally derived acetylcholine in the regulation of immune function
Reconciling neuronally and nonneuronally derived acetylcholine in the regulation of immune function
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DOI：
10.1111/j.1749-6632.2012.06516.x
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Horiguchi, Kazuhide
中科院分区：
文献类型：
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作者：
Kawashima, Koichiro;Fujii, Takeshi;Horiguchi, Kazuhide
包括淋巴细胞在内的免疫细胞表达毒蕈碱型和烟碱型乙酰胆碱（ACh）受体（分别为mAChR和nAChR），这些AChR的激动剂刺激导致细胞的功能和生化变化。然而，直到最近，作用于免疫细胞AChRs的ACh的起源仍然不清楚。1995年，我们在人类T细胞中鉴定了胆碱乙酰转移酶mRNA和蛋白，发现免疫T细胞活化通过增加ACh合成和AChR表达增强淋巴细胞胆碱能传递。我们还发现，M-1/M-5 mAChR信号上调IgG（1）和促炎细胞因子的产生，而α 7 nAChR信号具有相反的作用。这些结果表明，ACh合成的T细胞作为一个自分泌和/或旁分泌因子，通过AChRs免疫细胞调节免疫功能。此外，最近发现的内源性变构α 7 nAChR配体SLURP-1似乎也参与调节正常T细胞功能。
Immune cells, including lymphocytes, express muscarinic and nicotinic acetylcholine (ACh) receptors (mAChRs and nAChRs, respectively), and agonist stimulation of these AChRs causes functional and biochemical changes in the cells. The origin of the ACh that acts on immune cell AChRs has remained unclear until recently, however. In 1995, we identified choline acetyltransferase mRNA and protein in human T cells, and found that immunological T cell activation potentiated lymphocytic cholinergic transmission by increasing ACh synthesis and AChR expression. We also found that M-1/M-5 mAChR signaling upregulates IgG(1) and proinflammatory cytokine production, whereas alpha 7 nAChR signaling has the opposite effect. These findings suggest that ACh synthesized by T cells acts as an autocrine and/or paracrine factor via AChRs on immune cells to modulate immune function. In addition, a recently discovered endogenous allosteric alpha 7 nAChR ligand, SLURP-1, also appears to be involved in modulating normal T cell function.