TY - JOUR T1 - The <em>α</em>4 Nicotinic Receptor Promotes CD4<sup>+</sup> T-Cell Proliferation and a Helper T-Cell Immune Response JF - Molecular Pharmacology JO - Mol Pharmacol SP - 50 LP - 61 DO - 10.1124/mol.113.088484 VL - 85 IS - 1 AU - Jacob C. Nordman AU - Pretal Muldoon AU - Sarah Clark AU - M. Imad Damaj AU - Nadine Kabbani Y1 - 2014/01/01 UR - http://molpharm.aspetjournals.org/content/85/1/50.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 the circulation, spleen, bone marrow, and thymus, we find that nicotine promotes an increase in CD3+CD4+ cells via its activation of the α4 nAChR and regulation of G protein subunit o, G protein regulated–inducer of neurite outgrowth, and CDC42 signaling within T cells. In particular, nicotine is found to promote a helper T cell 2 adaptive immunologic response within T cells that is 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 -