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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

Genes & Immunity volume 12, pages 222–230 (2011)Cite this article

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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.

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  1. Departments of Dermatology and Biological Chemistry, Institute of Immunology, University of California Irvine, Irvine, CA, USA

    J Qian, V Galitovskiy, A I Chernyavsky, S Marchenko & S A Grando

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Correspondence to S A Grando.

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Presented in part at the 69th Annual Meeting of the Society for Investigative Dermatology, Montreal, Canada, May 6–9, 2009, and published in the form of an abstract in J Invest Dermatol 2009; 129 (Suppl. 1): S108, Abstr. #644.

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Qian, J., Galitovskiy, V., Chernyavsky, A. et al. 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. Genes Immun 12, 222–230 (2011). https://doi.org/10.1038/gene.2010.72

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