TY - JOUR T1 - The Alpha 4 Nicotinic Receptor Promotes CD4+ T-Cell Proliferation and a Th2 Immune Response JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.113.088484 SP - mol.113.088484 AU - Jacob C Nordman AU - Pretal Muldoon AU - Sarah Clark AU - Imad M Damaj AU - Nadine Kabbani Y1 - 2013/01/01 UR - http://molpharm.aspetjournals.org/content/early/2013/10/09/mol.113.088484.abstract N2 - Smoking is a common addiction and a leading cause of disease. Chronic nicotine exposure is known to activate nicotinic acetylcholine receptors (nAChRs) in immune cells. We demonstrate a novel role for α4 nAChRs in the effect of nicotine on T-cell proliferation and immunity. Using cell based sorting and proteomic analysis we define an α4 nAChR expressing helper T-cell population (α4+CD3+CD4+) and show that this group of cells is responsive to sustained nicotine exposure. In circulation, spleen, and thymus we find that nicotine promotes an increase in CD3+CD4+ cells via its activation of the α4 nAChR and regulation of Gαo, Gprin1, and CDC42 signaling within T-cells. In particular, nicotine is found to promote a Th2, adaptive, immunological response within T-cells, which was absent in α4-/- mice. We thus present a new mechanism of α4 nAChR signaling and immune regulation in T-cells, possibly accounting for the effect of smoking on the immune system. ER -