Abstract
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.
Footnotes
- Received July 15, 2013.
- Accepted October 9, 2013.
This work was supported by Jeffress Memorial Trust [J-953]; a Virginia Youth Tobacco Program grant (to N.K.); and the National Institutes of Health National Institute on Drug Abuse [Grant R01 DA-12610] (to M.I.D.).
↵This article has supplemental material available at molpharm.aspetjournals.org.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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