Cholinergic modulation of dendritic cell function

GABRIELA SALAMONE; GABRIELA LOMBARDI; SOLEDAD GORI; KAREN NAHMOD; CAROLINA JANCIC; MARÍA MARTA AMARAL; MÓNICA VERMEULEN; ALEJANDRO ESPAÑOL; MARÍA ELENA SALES; JORGE GEFFNER

JOURNAL OF NEUROIMMUNOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2011 vol. 236 p. 47 - 56

0165-5728

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 M3, M4 and M5, 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 alfa 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 alfa 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 alfa 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 alfa. ACh induced similar effects than carbachol; it stimulated the expression of HLA-DR and the production of TNF alfa, 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 alfa by DCs while inhibiting the production of TNF alfa and IL-12 triggered by LPS. These results support the existence of an autocrine/paracrine loop through which ACh modulates the function of DCs.