CONICET | Buscador de Institutos y Recursos Humanos

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels of the Cys-loop receptor family that serve as targets for acetylcholine and nicotine. nAChRs can be homomeric, which are assembled from five identical subunits, such as α7, or heteromeric, which are assembled from different subunits, such as α4β2. Although nAChRs have been studied mainly at the neuromuscular junction and in neurons, immune cells express several nAChR subunits but the functional relevance of the extra-neuronal cholinergic system remains still undefined. Previously, we demonstrated that human natural killer (NK) cells express α7 nAChR whose expression levels increase during NK stimulation with IL-12, IL-18, and IL-15. Activation of α7 down-regulates NKG2D receptors, and decreases NKG2D-dependent cell-mediated cytotoxicity and IFN-γ production. In the present study, we investigated the expression of α4β2 nAChR in human NK cells as well as its regulation in their functions. By RT-PCR, we detected in freshly isolated human NK cells mRNA corresponding to α4 and β2 nAChR subunits. Upon stimulation of NK cells with IL-12, IL-18, and IL-15 for 48h, the mRNA determined by qPCR and cell surface expression determined by flow cytometry of α4 nAChR did not change significantly, whereas those of β2 slightly increased with respect to fresh cells. Activation of α4β2 nAChR with the specific agonist 5-Iodo-A-85380 did not affect the expression of some major NK cell activating receptors, such as NKG2D, NKp46, and DNAM-1, as well as the levels of perforins and IFN-γ production. Activation of α4β2 nAChR by its specific agonist 5-Iodo-A-85380 did not affect the expression of CCR7 or CD62L, which are indicators of the migratory potential of NK cells to lymph nodes. Taken together, our results show that α4β2 is neither regulated by NK stimulation nor involved in NK cell effector functions, thus indicating that, among nAChRs, α7 is a central player in NK cell physiology.