Expression and functional role of neuronal alpha7 nicotinic receptor in human NK cells

TORRES, N.I.; ZANETTI, S.R.; ZWIRNER, N.W.; ZIBLAT, A.; BOUZAT, C.B.

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

An entire neuronal cholinergic system has been detected in immune cells, but the functional relevance of this extra- neuronal cholinergic system remains ill-de ned. The alpha7 nicotinic receptor is one of the most abundant in the central nervous system and it is emerging as an important drug target for neurological disorders. Alpha7 is also present in immune cells, and it is an important player of the cholinergic anti-in ammatory pathway which links the nervous with the immune systems. Natural killer (NK) cells display cytotoxic activity against susceptible target cells and modulate innate and adaptive immune responses. Here, we show that human NK cells also express alpha7. Both alpha7 mRNA and protein levels increase during NK stimulation with cytokines. Exposure of cytokine-stimulated NK cells to PNU-282987, a speci c alpha7 agonist, increases intracellular calcium concentration mainly by its release from intracellular stores. The calcium response is enhanced in the presence of PNU-120596, a speci c positive allosteric modulator. Activation of alpha7 decreases NF-kappaB levels and nuclear mobilization, downregulates a potent activating receptor of NK cells, decreases cell-mediated cytotoxicity, IFN-gamma production and DC maturation. Thus, our results demonstrate that activation of alpha7 leads to anti-in ammatory actions on NK cells, and suggest that modulation of its activity in NK cells may constitute a novel target to regulate the immune response.