Lymphocyte-derived ACh regulates local innate but not adaptive immunity
Lymphocyte-derived ACh regulates local innate but not adaptive immunity
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DOI：
10.1073/pnas.1221655110
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发表时间：
2013-01-22
影响因子：
11.1
通讯作者：
Mak, Tak W.
中科院分区：
文献类型：
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作者：
Reardon, Colin;Duncan, Gordon S.;Mak, Tak W.
适当控制免疫反应是健康的关键决定因素。在这里，我们发现B细胞和其他影响先天免疫的免疫细胞表达胆碱乙酰转移酶（ChAT）并产生ACh。ChAT表达发生在粘膜相关淋巴组织，随后微生物定植，并通过抗生素治疗减少。myd88依赖性toll样受体以瞬时方式上调ChAT。与先前描述的CD4(+) t细胞群在去甲肾上腺素刺激下释放乙酰胆碱不同，ChAT(+) B细胞在硫酸化胆囊收缩素刺激下释放乙酰胆碱，但不释放去甲肾上腺素。在不依赖迷走神经的无菌内毒素血症中，产生乙酰胆碱的b细胞减少腹膜中性粒细胞的募集，而不影响先天免疫细胞的激活。乙酰胆碱处理的内皮细胞在体外以毒蕈碱受体依赖的方式降低内皮细胞粘附分子的表达。尽管有这种能力，ChAT(+) B细胞在体内不能抑制效应t细胞的功能。因此，淋巴细胞产生的ACh具有特异性功能，ChAT(+) B细胞控制着中性粒细胞的局部募集。
Appropriate control of immune responses is a critical determinant of health. Here, we show that choline acetyltransferase (ChAT) is expressed and ACh is produced by B cells and other immune cells that have an impact on innate immunity. ChAT expression occurs in mucosal-associated lymph tissue, subsequent to microbial colonization, and is reduced by antibiotic treatment. MyD88-dependent Toll-like receptor up-regulates ChAT in a transient manner. Unlike the previously described CD4(+) T-cell population that is stimulated by norepinephrine to release ACh, ChAT(+) B cells release ACh after stimulation with sulfated cholecystokinin but not norepinephrine. ACh-producing B-cells reduce peritoneal neutrophil recruitment during sterile endotoxemia independent of the vagus nerve, without affecting innate immune cell activation. Endothelial cells treated with ACh in vitro reduced endothelial cell adhesion molecule expression in a muscarinic receptor-dependent manner. Despite this ability, ChAT(+) B cells were unable to suppress effector T-cell function in vivo. Therefore, ACh produced by lymphocytes has specific functions, with ChAT(+) B cells controlling the local recruitment of neutrophils.