title: Lymphocyte-derived ACh regulates local innate but not adaptive immunity.
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 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.
authors.affiliation: Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1.
authors.forename: Colin
authors.initials: C
authors.lastname: Reardon
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Duncan
authors.forename: Anne
authors.initials: A
authors.lastname: Brüstle
authors.forename: Dirk
authors.initials: D
authors.lastname: Brenner
authors.forename: Michael W
authors.initials: MW
authors.lastname: Tusche
authors.forename: Peder S
authors.initials: PS
authors.lastname: Olofsson
authors.forename: Peder
authors.initials: P
authors.lastname: Olofsson
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rosas-Ballina
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tracey
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis*; D056704:Adaptive Immunity / Q000502:physiology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D054892:Metagenome / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015213:Neuroimmunomodulation; D011247:Pregnancy; D017981:Receptors, Neurotransmitter / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D017981:Receptors, Neurotransmitter; D011993:Recombinant Fusion Proteins; D051193:Toll-Like Receptors; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine