Lymphocyte-derived ACh regulates local innate but not adaptive immunity

C Reardon, GS Duncan, A Brüstle… - Proceedings of the …, 2013 - National Acad Sciences
C Reardon, GS Duncan, A Brüstle, D Brenner, MW Tusche, PS Olofsson, M Rosas-Ballina
Proceedings of the National Academy of Sciences, 2013National Acad Sciences
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 …
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.
National Acad Sciences