title: Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naïve CD4 T cells toward the Th1, Th2 and Th17 lineages.
abstract: Acetylcholine (ACh) regulates vital functions of T cells by acting on the nicotinic and muscarinic classes of cholinergic receptors, nAChR and mAChRs, respectively. This study was performed in murine splenic T cells. In freshly isolated CD4 and CD8 T cells, we detected mRNAs encoding α5, α9, α10, β1, β2, β4 nAChR subunits and M₁, M₃, M₄ and M₅ mAChR subtypes, whereas α2 was detected only in CD8 T cells. In vitro activation of CD4 T cells through T-cell receptor (TCR)/CD3 cross-linking was associated with the appearance of α4 and α7, upregulation of α5, α10, β4, M₁ and M₅ and downregulation of α9 and β2, whereas in vitro activation of CD8 T cells also featured the appearance of α4 and α7, as well as upregulation of α2, α5, β4, M₁ and M₄, and downregulation of α10, β1, β2 and M₃. In vitro polarization toward T helper (Th) 1 lineage was associated with a decrease of β2, β4 and M₃ expression; that toward Th2 cells with downregulation of α9 and M₃, and upregulation of M₁ and M₅; and that toward Th17 phenotype with downregulation of α9, α10, β2 and M₃ mAChR. Polarized T cells also expressed α4, but not α1, α2, α3, α6, β3 or M₂. To determine the role of cholinergic receptors in mediating the immunoregulatory action of autocrine/paracrine ACh, we analyzed the effects of nicotinic and muscarinic agonists±antagonists on cytokine production in the CD4+CD62L+ T cells co-stimulated via TCR/CD3 cross-linking. The nicotinergic stimulation upregulated interferon-γ (IFN-γ) and downregulated interleukin (IL)-17 secretion, whereas the muscarinic stimulation enhanced IL-10 and IL-17 and inhibited INF-γ secretion. These results demonstrated plasticity of the T-cell cholinergic system.
authors.affiliation: Department of Dermatology, Institute of Immunology, University of California Irvine, Irvine, CA 92697, USA.
authors.forename: J
authors.initials: J
authors.lastname: Qian
authors.forename: V
authors.initials: V
authors.lastname: Galitovskiy
authors.forename: A I
authors.initials: AI
authors.lastname: Chernyavsky
authors.forename: S
authors.initials: S
authors.lastname: Marchenko
authors.forename: S A
authors.initials: SA
authors.lastname: Grando
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011950:Receptors, Cholinergic