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

GORI MS; MOVERER L; SABBIONE F; JANCIC C; SCORDO W; TOWSTYKA N; ALCAIN J; GEFFNER J; VERMEULEN M; SALAMONE G

Mar del Plata

Congreso; Reunión Conjunta SAIC-SAI-SAFE 2016; 2016

Acetylcholine ACh is the most important parasympathetic neurotransmitter and increasing evidence indicates that it is able to modulate the immune response. 9e have previously shoYn that dendritic cells &C express muscarinic receptors, as Yell as the enzymes responsible for the synthesis and degradation of ACh. Then, Ye proved that ACh polarizes &C toYard a Thpromoting profile, increasing 1:L expression and moreover, reinforces the expression of 1:L and C& on &C, as Yell as +L and TNF-αproduction induced by the Thpromoting cytoMine, thymic stromal lymphopoietin TSL2. This molecule plays a Mey role in the induction and maintenance of allergic responses at the epithelial surfaces. +n this YorM, Ye evaluated Yhich cholinergic receptors muscarinic or nicotinic Yere involved in the promotion of TSL2mediated effects induced by ACh on &C. For this, C& cells Yere isolated from peripheral blood mononuclear cells of healthy adult nonsmoMer donors by positive selection /iltenyi and obtained monocytes Yere cultured for days Yith )/CSF+L. &C Yere preincubated for min Yith or Yithout nonselective muscarinic atropine, AT / and nicotinic mecamylamine, // / receptor antagonists. Then, &C Yere cultured for h Yith ACh /, TSL2 ng/ml, or ACh plus TSL2. 9e shoYed that AT, but not //, significantly inhibited the enhancing effect induced by ACh on the ability of TSL2 to increase 1:L p. and C& p. expression, as Yell as the production of T0Fαp. and +L p.. Surprisingly, AT inhibited the 1:L and C& expression induced by TSL2, suggesting the modulation of the &C cholinergic system by this cytoMine. These results shoY the involvement of muscarinic receptors in the polarization of &C toYard a Thpromoting profile induced by both TSLP and ACh, suggesting that anticholinergics could also protect the airYay in the course of inflammatory chronic diseases by the inhibition of this &C profile.