Abstract
alpha7 nicotinic acetylcholine receptor (α7nAChR) has been recently found in several non-neuronal cells and described as an important regulator of cellular function. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the active suppression of autoimmunity. The present study was undertaken to investigate whether naturally occurring Tregs expressed α7nAChR and the functionary role of this receptor in controlling suppressive activity of these cells. It was found that CD4+CD25+Tregs from naïve C57BL/6J mice positively expressed α7nAChR, and its activation by nicotine enhanced suppressive capacity of Tregs. Nicotine-stimulation up-regulated the expression of cytotoxic T lymphocyte-associated antigen (CTLA)-4 and forkhead/winged helix transcription factor p3 (Foxp3) on Tregs but had no effect on the production of interleukin (IL)-10 and transforming growth factor (TGF)-beta1 by Tregs. In the supernatants of CD4+CD25+Tregs/CD4+CD25-T cell cocultures, concentration of IL-2 was observed to be decreased in nicotine-stimulated groups, but nicotine-stimulation had no effect on the ratio of IL-4/interferon (IFN)-gamma, which partially representing T cell polarization. The above mentioned effects of nicotine were reversed by a selective α7nAChR antagonist, alpha-bungarotoxin. Additionally, the ratio of IL-4/IFN-γ was increased by treatment with alpha-bungarotoxin. It is concluded that nicotine might increase Treg-mediated immune suppression of lymphocytes via α7nAChR. The effect is related to up-regulation of CTLA-4 as well as Foxp3 expression and decreased IL-2 secretion in CD4+CD25+Treg/CD4+CD25-T cell coculture supernatants. α7nAChR appears to be a critical regulator for immune suppressive function of CD4+CD25+Tregs.
- CD4+CD25+ regulatory T cells
- alpha7 nicotinic acetylcholine receptor
- cytotoxic T lymphocyte-associated antigen-4
- forkhead/winged helix transcription factor p3
- interleukin-2
- nicotine
- Received May 8, 2010.
- Revision received September 14, 2010.
- Accepted September 14, 2010.
- The American Society for Pharmacology and Experimental Therapeutics