ACETYLCHOLINE REINFORCES THE POLARIZATION OF DENDRITIC CELLS TOWARD A TH2-PROMOTING PROFILE INDUCED BY TSLP THROUGH MUSCARINIC RECEPTORS.

FLORENCIA SABBIONE; NADIA TOWSTYKA; MÓNICA VERMEULEN; LUCIANA MOVERER; SOLEDAD GORI; WALTER SCORDO; CAROLINA JANCIC; JORGE GEFFNER; JULIETA ALCAIN; GABRIELA SALAMONE

Mar del Plata

Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2016

SAI

Acetylcholine (ACh) is the most important parasympatheticneurotransmitter and increasing evidence indicates that it is ableto modulate the immune response. We have previously shown thatdendritic cells (DC) express muscarinic receptors, as well as theenzymes responsible for the synthesis and degradation of ACh.Then, we proved that ACh polarizes DC toward a Th2-promotingprofile, increasing OX40L expression and moreover, reinforcesthe expression of OX40L and CD83 on DC, as well as IL-8 andTNF-α production induced by the Th2-promoting cytokine, thymicstromal lymphopoietin (TSLP). This molecule plays a key rolein the induction and maintenance of allergic responses at theepithelial surfaces. In this work, we evaluated which cholinergicreceptors (muscarinic or nicotinic) were involved in the promotionof 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) andobtained monocytes were cultured for 5 days with GM-CSF+IL-4.DC were pre-incubated for 30 min with or without non-selectivemuscarinic (atropine, AT 10-7M) and nicotinic (mecamylamine,MM 10-7M) receptor antagonists. Then, DC were cultured for 18h with ACh (10-8M), TSLP (15 ng/ml), or ACh plus TSLP. Weshowed that AT, but not MM, significantly inhibited the enhancingeffect induced by ACh on the ability of TSLP to increase OX40L(p