title: Cholinergic modulation of dendritic cell function.
abstract: Dendritic cells (DCs) are highly specialized antigen-presenting cells with a unique ability to activate resting T lymphocytes. Acetylcholine (ACh) is the primary parasympathetic neurotransmitter and also a non-neural paracrine factor produced by different cells. Here, we analyzed the expression of the cholinergic system in DCs. We found that DCs express the muscarinic receptors M(3), M(4) and M(5), as well as the enzymes responsible for the synthesis and degradation of ACh, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), respectively. Differentiation of DCs in the presence of the cholinergic agonist carbachol, the synthetic analog of ACh, resulted in an increased expression of HLA-DR and CD86 and the stimulation of TNF-α and IL-8 production. All these effects were prevented by atropine, a muscarinic ACh receptor (mAChR) antagonist. Carbachol, was also able to modulate the function of DCs when added after the differentiation is accomplished; it increased the expression of HLA-DR, improved the T cell priming ability of DCs, and stimulated the production of TNF-α but not IL-12 or IL-10. By contrast, carbachol significantly inhibited the stimulation of HLA-DR expression and the enhancement in the T cell priming ability of DCs triggered by LPS. Interestingly, the TNF-α antagonist etanercept completely prevented the increased expression of HLA-DR induced by carbachol, suggesting that it promotes the phenotypic maturation of DCs by stimulating the production of TNF-α. ACh induced similar effects than carbachol; it stimulated the expression of HLA-DR and the production of TNF-α, while inhibiting the stimulation of HLA-DR expression and IL-12 production triggered by LPS. Similarly, neostigmine, an inhibitor of AChE, also stimulated the expression of HLA-DR and the production of TNF-α by DCs while inhibiting the production of TNF-α and IL-12 triggered by LPS. These results support the existence of an autocrine/paracrine loop through which ACh modulates the function of DCs.
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Hematológicas and Instituto de Estudios Oncológicos Fundación Maissa, Academia Nacional de Medicina, Argentina. salamone.gabriela@gmail.com
authors.forename: Gabriela
authors.initials: G
authors.lastname: Salamone
authors.forename: Gabriela
authors.initials: G
authors.lastname: Lombardi
authors.forename: Soledad
authors.initials: S
authors.lastname: Gori
authors.forename: Karen
authors.initials: K
authors.lastname: Nahmod
authors.forename: Carolina
authors.initials: C
authors.lastname: Jancic
authors.forename: María Marta
authors.initials: MM
authors.lastname: Amaral
authors.forename: Mónica
authors.initials: M
authors.lastname: Vermeulen
authors.forename: Alejandro
authors.initials: A
authors.lastname: Español
authors.forename: María Elena
authors.initials: ME
authors.lastname: Sales
authors.forename: Jorge
authors.initials: J
authors.lastname: Geffner
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000110:Acetylcholinesterase / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000502:physiology; D018679:Cholinergic Agonists / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D011976:Receptors, Muscarinic / Q000502:physiology
chemical_list: D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D011976:Receptors, Muscarinic; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine