Lymphocyte-derived ACh regulates local innate but not adaptive immunity

Colin Reardon, Gordon S. Duncan, Anne Brüstle, Dirk Brenner, Michael W. Tusche, Peder Olofsson, Mauricio Rosas-Ballina, Kevin J. Tracey, Tak W. Mak

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

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 Tolllike 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. AChproducing 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 cellswere 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.

Original languageEnglish (US)
Pages (from-to)1410-1415
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number4
DOIs
StatePublished - Jan 22 2013
Externally publishedYes

ASJC Scopus subject areas

  • General

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    Reardon, C., Duncan, G. S., Brüstle, A., Brenner, D., Tusche, M. W., Olofsson, P., Rosas-Ballina, M., Tracey, K. J., & Mak, T. W. (2013). Lymphocyte-derived ACh regulates local innate but not adaptive immunity. Proceedings of the National Academy of Sciences of the United States of America, 110(4), 1410-1415. https://doi.org/10.1073/pnas.1221655110