TY - JOUR
T1 - Expression and Function of Nicotinic Acetylcholine Receptors in Induced Regulatory T Cells
AU - Nakata, Yuichiro
AU - Miura, Kento
AU - Yamasaki, Norimasa
AU - Ogata, Sawako
AU - Miura, Shuka
AU - Hosomi, Naohisa
AU - Kaminuma, Osamu
N1 - Funding Information:
Funding: This research was funded by Taiju Life Social Welfare Foundation and Smoking Research Foundation grants provided to O.K. and by a Joint Research Grant from the Research Center for Radiation Disaster Medical Science to Y.N.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - A contribution of the cholinergic system to immune cell function has been suggested, though the role of nicotine and its receptors in T cells, especially regulatory T (Treg) cells, is unclear. We herein investigated the expression and function of nicotinic acetylcholine receptors (nAChRs) in murine-induced Treg (iTreg) cells. Upon differentiation of naive BALB/c T cells into iTreg cells and other T-cell subsets, the effect of nicotine on cytokine production and proliferation of iTreg cells was examined. The expression of nAChRs and its regulatory mechanisms were comparatively ana-lyzed among T-cell subsets. Stimulation-induced transforming growth factor-β1 (TGF-β1) production of iTreg cells was suppressed by nicotine, whereas interleukin (IL)-10 production and proliferation was not affected. α2-, α5-, α9-, and β2-nAChRs were differentially expressed in naive, Th1, Th2, Th9, Th17, and iTreg cells. Among these cell types, the α9-nAChR was particularly upregulated in iTreg cells via its gene promoter, but not through tri-methylation at the 4th lysine residue of the histone H3-dependent mechanisms. We conclude that the immunoregulatory role of Treg cells is modified by the cholinergic system, probably through the characteristic expression of nAChRs.
AB - A contribution of the cholinergic system to immune cell function has been suggested, though the role of nicotine and its receptors in T cells, especially regulatory T (Treg) cells, is unclear. We herein investigated the expression and function of nicotinic acetylcholine receptors (nAChRs) in murine-induced Treg (iTreg) cells. Upon differentiation of naive BALB/c T cells into iTreg cells and other T-cell subsets, the effect of nicotine on cytokine production and proliferation of iTreg cells was examined. The expression of nAChRs and its regulatory mechanisms were comparatively ana-lyzed among T-cell subsets. Stimulation-induced transforming growth factor-β1 (TGF-β1) production of iTreg cells was suppressed by nicotine, whereas interleukin (IL)-10 production and proliferation was not affected. α2-, α5-, α9-, and β2-nAChRs were differentially expressed in naive, Th1, Th2, Th9, Th17, and iTreg cells. Among these cell types, the α9-nAChR was particularly upregulated in iTreg cells via its gene promoter, but not through tri-methylation at the 4th lysine residue of the histone H3-dependent mechanisms. We conclude that the immunoregulatory role of Treg cells is modified by the cholinergic system, probably through the characteristic expression of nAChRs.
KW - Acetylcholine receptors
KW - Histone modification
KW - Immune regulation
KW - Nicotine
KW - T cell
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U2 - 10.3390/ijms23031779
DO - 10.3390/ijms23031779
M3 - Article
C2 - 35163704
AN - SCOPUS:85123949207
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 3
M1 - 1779
ER -