Acetylcholine reinforces the polarization of dendritic cells toward a Th2-promoting profile induced by TSLP through muscarinic receptors

GORI, MARÍA SOLEDAD; MOVERER, LUCIANA; SABBIONE, FLORENCIA; JANCIC, CAROLINA C.; SCORDO, WALTER; TOWSTYKA, NADIA YASMÍN; ALCAIN, JULIETA; GEFFNER, JORGE R.; VERMEULEN, MÓNICA; SALAMONE, GABRIELA

Congreso; 64 Reunión Anual de la Sociedad Argentina de Inmunología; 2016

Acetylcholine (ACh) is the most important parasympathetic neurotransmitter and increasing evidence indicates that it is able to modulate the immune response. We have previously shown that dendritic cells (DC) express muscarinic receptors, as well as the enzymes responsible for the synthesis and degradation of ACh. Then, we proved that ACh polarizes DC toward a Th2-promoting profile, increasing OX40L expression and moreover, reinforces the expression of OX40L and CD83 on DC, as well as IL-8 and TNF-α production induced by the Th2-promoting cytokine, thymic stromal lymphopoietin (TSLP). This molecule plays a key role in the induction and maintenance of allergic responses at theepithelial surfaces. In this work, we evaluated which cholinergic receptors (muscarinic or nicotinic) were involved in the promotion of TSLP-mediated effects induced by ACh on DC. For this, CD14+ cells were isolated from peripheral blood mononuclear cells of healthy adult nonsmoker donors by positive selection (Miltenyi) and obtained monocytes were cultured for 5 days with GM-CSF+IL-4. DC were pre-incubated for 30 min with or without non-selective muscarinic (atropine, AT 10-7M) and nicotinic (mecamylamine, MM 10-7M) receptor antagonists. Then, DC were cultured for 18 h with ACh (10-8M), TSLP (15 ng/ml), or ACh plus TSLP. We showed that AT, but not MM, significantly inhibited the enhancing effect induced by ACh on the ability of TSLP to increase OX40L (p<0.05) and CD83 (p<0.05) expression, as well as the production of TNF-α (p<0.01) and IL-8 (p<0.0001). Surprisingly, AT inhibited the OX40L and CD83 expression induced by TSLP, suggesting the modulation of the DC cholinergic system by this cytokine. These results show the involvement of muscarinic receptors in the polarization of DC toward a Th2-promoting profile induced by both TSLP and ACh, suggesting that anticholinergics could also protect the airway in the course of inflammatory chronic diseases by the inhibition of this DC profile.