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Stimulation of α7 nicotinic acetylcholine receptor by nicotine increases suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro.
J Pharmacol Exp Ther 2010; 335(3):553-61JP

Abstract

α7 Nicotinic acetylcholine receptor (α7 nAChR) has been found in several non-neuronal cells and is 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 investigated whether naturally occurring Tregs expressed α7 nAChR and investigated the functionary role of this receptor in controlling suppressive activity of these cells. We found that CD4(+)CD25(+) Tregs from naive C57BL/6J mice positively expressed α7 nAChR, and its activation by nicotine enhanced the 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-β1 by Tregs. In the supernatants of CD4(+)CD25(+) Tregs/CD4(+)CD25(-) T-cell cocultures, we observed a decrease in the concentration of IL-2 in nicotine-stimulated groups, but nicotine stimulation had no effect on the ratio of IL-4/interferon (IFN)-γ, which partially represented T-cell polarization. The above-mentioned effects of nicotine were reversed by a selective α7 nAChR antagonist, α-bungarotoxin. In addition, the ratio of IL-4/IFN-γ was increased by treatment with α-bungarotoxin. We conclude that nicotine might increase Treg-mediated immune suppression of lymphocytes via α7 nAChR. The effect is related to the up-regulation of CTLA-4 as well as Foxp3 expression and decreased IL-2 secretion in CD4(+)CD25(+) Tregs/CD4(+)CD25(-) T-cell coculture supernatants. α7 nAChR seems to be a critical regulator for immunosuppressive function of CD4(+)CD25(+) Tregs.

Authors+Show Affiliations

Emergency Department, General Hospital of Beijing Military Area Command, Beijing, People’s Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20843956

Citation

Wang, Da-wei, et al. "Stimulation of Α7 Nicotinic Acetylcholine Receptor By Nicotine Increases Suppressive Capacity of Naturally Occurring CD4+CD25+ Regulatory T Cells in Mice in Vitro." The Journal of Pharmacology and Experimental Therapeutics, vol. 335, no. 3, 2010, pp. 553-61.
Wang DW, Zhou RB, Yao YM, et al. Stimulation of α7 nicotinic acetylcholine receptor by nicotine increases suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro. J Pharmacol Exp Ther. 2010;335(3):553-61.
Wang, D. W., Zhou, R. B., Yao, Y. M., Zhu, X. M., Yin, Y. M., Zhao, G. J., ... Sheng, Z. Y. (2010). Stimulation of α7 nicotinic acetylcholine receptor by nicotine increases suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro. The Journal of Pharmacology and Experimental Therapeutics, 335(3), pp. 553-61. doi:10.1124/jpet.110.169961.
Wang DW, et al. Stimulation of Α7 Nicotinic Acetylcholine Receptor By Nicotine Increases Suppressive Capacity of Naturally Occurring CD4+CD25+ Regulatory T Cells in Mice in Vitro. J Pharmacol Exp Ther. 2010;335(3):553-61. PubMed PMID: 20843956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stimulation of α7 nicotinic acetylcholine receptor by nicotine increases suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro. AU - Wang,Da-wei, AU - Zhou,Rong-bin, AU - Yao,Yong-ming, AU - Zhu,Xiao-mei, AU - Yin,Yi-mei, AU - Zhao,Guang-ju, AU - Dong,Ning, AU - Sheng,Zhi-yong, Y1 - 2010/09/15/ PY - 2010/9/17/entrez PY - 2010/9/17/pubmed PY - 2011/2/4/medline SP - 553 EP - 61 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 335 IS - 3 N2 - α7 Nicotinic acetylcholine receptor (α7 nAChR) has been found in several non-neuronal cells and is 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 investigated whether naturally occurring Tregs expressed α7 nAChR and investigated the functionary role of this receptor in controlling suppressive activity of these cells. We found that CD4(+)CD25(+) Tregs from naive C57BL/6J mice positively expressed α7 nAChR, and its activation by nicotine enhanced the 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-β1 by Tregs. In the supernatants of CD4(+)CD25(+) Tregs/CD4(+)CD25(-) T-cell cocultures, we observed a decrease in the concentration of IL-2 in nicotine-stimulated groups, but nicotine stimulation had no effect on the ratio of IL-4/interferon (IFN)-γ, which partially represented T-cell polarization. The above-mentioned effects of nicotine were reversed by a selective α7 nAChR antagonist, α-bungarotoxin. In addition, the ratio of IL-4/IFN-γ was increased by treatment with α-bungarotoxin. We conclude that nicotine might increase Treg-mediated immune suppression of lymphocytes via α7 nAChR. The effect is related to the up-regulation of CTLA-4 as well as Foxp3 expression and decreased IL-2 secretion in CD4(+)CD25(+) Tregs/CD4(+)CD25(-) T-cell coculture supernatants. α7 nAChR seems to be a critical regulator for immunosuppressive function of CD4(+)CD25(+) Tregs. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/20843956/Stimulation_of_α7_nicotinic_acetylcholine_receptor_by_nicotine_increases_suppressive_capacity_of_naturally_occurring_CD4+CD25+_regulatory_T_cells_in_mice_in_vitro_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=20843956 DB - PRIME DP - Unbound Medicine ER -