首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Lymphocyte-derived ACh regulates local innate but not adaptive immunity
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Lymphocyte-derived ACh regulates local innate but not adaptive immunity

机译:淋巴细胞衍生的乙酰胆碱可调节局部先天性而非适应性免疫

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摘要

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 Toil-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.
机译:适当控制免疫反应是健康的关键因素。在这里,我们显示胆碱乙酰基转移酶(ChAT)被表达,ACh由B细胞和其他对先天免疫有影响的免疫细胞产生。在微生物定殖之后,ChAT表达发生在粘膜相关的淋巴组织中,并通过抗生素治疗而降低。 MyD88依赖的Toil样受体以瞬时方式上调ChAT。与先前描述的被去甲肾上腺素刺激释放ACh的CD4 + T细胞群不同,ChAT + + B细胞在被硫酸化的胆囊收缩素刺激后不释放ACh。产生ACh的B细胞可在不依赖迷走神经的无菌内毒素血症期间减少腹膜中性粒细胞的募集,而不会影响先天免疫细胞的激活。体外用ACh处理的内皮细胞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细胞仍无法在体内抑制效应T细胞功能。因此,淋巴细胞产生的ACh具有特定功能,ChAT〜+ B细胞控制嗜中性粒细胞的局部募集。

著录项

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  • 作者单位

    Department of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;

    Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1;

    Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1;

    Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1,Institut fuer Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universitat Munchen, 81675 Munich, Germany;

    Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1;

    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, NY 11030;

    Infection Biology Biozentrum, University of Basel, CH-4056 Basel, Switzerland;

    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, NY 11030;

    Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    colitis i inflammatory reflex; regulatory T cells; sepsis;

    机译:结肠炎;炎症反射;调节性T细胞;败血症;
  • 入库时间 2022-08-18 00:39:50

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