TY - JOUR
T1 - Lymphocyte-derived ACh regulates local innate but not adaptive immunity
AU - Reardon, Colin
AU - Duncan, Gordon S.
AU - Brüstle, Anne
AU - Brenner, Dirk
AU - Tusche, Michael W.
AU - Olofsson, Peder
AU - Rosas-Ballina, Mauricio
AU - Tracey, Kevin J.
AU - Mak, Tak W.
PY - 2013/1/22
Y1 - 2013/1/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84872835053&partnerID=8YFLogxK
U2 - 10.1073/pnas.1221655110
DO - 10.1073/pnas.1221655110
M3 - Article
C2 - 23297238
AN - SCOPUS:84872835053
SN - 0027-8424
VL - 110
SP - 1410
EP - 1415
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -