title: Reconciling neuronally and nonneuronally derived acetylcholine in the regulation of immune function.
abstract: Immune cells, including lymphocytes, express muscarinic and nicotinic acetylcholine (ACh) receptors (mAChRs and nAChRs, respectively), and agonist stimulation of these AChRs causes functional and biochemical changes in the cells. The origin of the ACh that acts on immune cell AChRs has remained unclear until recently, however. In 1995, we identified choline acetyltransferase mRNA and protein in human T cells, and found that immunological T cell activation potentiated lymphocytic cholinergic transmission by increasing ACh synthesis and AChR expression. We also found that M(1) /M(5)  mAChR signaling upregulates IgG(1)  and proinflammatory cytokine production, whereas α7 nAChR signaling has the opposite effect. These findings suggest that ACh synthesized by T cells acts as an autocrine and/or paracrine factor via AChRs on immune cells to modulate immune function. In addition, a recently discovered endogenous allosteric α7 nAChR ligand, SLURP-1, also appears to be involved in modulating normal T cell function.
authors: Department of Molecular Pharmacology, Kitasato University School of Pharmacy, Tokyo, Japan. koichiro-jk@piano.ocn.ne.jp
authors: Koichiro
authors: K
authors: Kawashima
authors: Takeshi
authors: T
authors: Fujii
authors: Yasuhiro
authors: Y
authors: Moriwaki
authors: Hidemi
authors: H
authors: Misawa
authors: Kazuhide
authors: K
authors: Horiguchi
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D000818:Animals; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015213:Neuroimmunomodulation; D009474:Neurons / Q000276:immunology*; D012333:RNA, Messenger / Q000276:immunology / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000276:immunology / Q000378:metabolism; D043642:Receptor, Muscarinic M5 / Q000276:immunology / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D000950:Antigens, Ly; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D007074:Immunoglobulin G; D012333:RNA, Messenger; D043643:Receptor, Muscarinic M1; D043642:Receptor, Muscarinic M5; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; C048963:SLURP1 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002795:Choline O-Acetyltransferase; D014568:Urokinase-Type Plasminogen Activator; D000109:Acetylcholine