The α4 nicotinic receptor promotes CD4+ T-cell proliferation and a helper T-cell immune response
| Autor: | Nadine Kabbani, Jacob C. Nordman, Pretal P. Muldoon, Sarah G. Clark, M. Imad Damaj |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Nicotine CD3 Complex T cell CD3 T-Lymphocytes Bone Marrow Cells Thymus Gland Receptors Nicotinic Interleukin 21 Mice Immune system medicine Animals Receptor cdc42 GTP-Binding Protein Pharmacology Mice Knockout biology T-Lymphocytes Helper-Inducer Articles Cell biology Mice Inbred C57BL medicine.anatomical_structure Nicotinic agonist Immunology CD4 Antigens biology.protein Molecular Medicine Cytokines Signal transduction Spleen medicine.drug Signal Transduction |
| Zdroj: | Molecular pharmacology. 85(1) |
| ISSN: | 1521-0111 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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