title: Stimulation of α7 nicotinic acetylcholine receptor by nicotine increases suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro.
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.affiliation: Emergency Department, General Hospital of Beijing Military Area Command, Beijing, People’s Republic of China.
authors.forename: Da-wei
authors.initials: DW
authors.lastname: Wang
authors.forename: Rong-bin
authors.initials: RB
authors.lastname: Zhou
authors.forename: Yong-ming
authors.initials: YM
authors.lastname: Yao
authors.forename: Xiao-mei
authors.initials: XM
authors.lastname: Zhu
authors.forename: Yi-mei
authors.initials: YM
authors.lastname: Yin
authors.forename: Guang-ju
authors.initials: GJ
authors.lastname: Zhao
authors.forename: Ning
authors.initials: N
authors.lastname: Dong
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Sheng
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D049109:Cell Proliferation; D018920:Coculture Techniques; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000378:metabolism / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D015703:Antigens, CD; D002038:Bungarotoxins; D060908:CTLA-4 Antigen; C579166:Chrna7 protein, mouse; C556707:Ctla4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D053773:Transforming Growth Factor beta1; D064569:alpha7 Nicotinic Acetylcholine Receptor; D016753:Interleukin-10; D015847:Interleukin-4; D009538:Nicotine; D007371:Interferon-gamma