1. The Sympathetic Nervous System Mitigates CNS Autoimmunity via β2-Adrenergic Receptor Signaling in Immune Cells
- Author
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Marcia G. Guereschi, Juliana Terzi Maricato, Filipe M. de Melo, Leandro Pires Araujo, Patricia Chakur Brum, Maisa C. Takenaka, Francisco J. Quintana, Alexandre S. Basso, and Vanessa M. Nascimento
- Subjects
0301 basic medicine ,Sympathetic nervous system ,animal structures ,Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,Sympathetic Nervous System ,T-Lymphocytes ,Disease ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Autoimmunity ,RATOS ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Immune system ,medicine ,Animals ,Neurotransmitter ,Receptor ,lcsh:QH301-705.5 ,Mice, Knockout ,Immunity, Cellular ,business.industry ,Multiple sclerosis ,Experimental autoimmune encephalomyelitis ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,lcsh:Biology (General) ,Immunology ,Cytokines ,Receptors, Adrenergic, beta-2 ,business ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Summary: Noradrenaline (NE), the main neurotransmitter released by sympathetic nerve terminals, is known to modulate the immune response. However, the role of the sympathetic nervous system (SNS) on the development of autoimmune diseases is still unclear. Here, we report that the SNS limits the generation of pathogenic T cells and disease development in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). β2-Adrenergic receptor (Adrb2) signaling limits T cell autoimmunity in EAE through a mechanism mediated by the suppression of IL-2, IFN-γ, and GM-CSF production via inducible cAMP early repressor (ICER). Accordingly, the lack of Adrb2 signaling in immune cells is sufficient to abrogate the suppressive effects of SNS activity, resulting in increased pathogenic T cell responses and EAE development. Collectively, these results uncover a suppressive role for the SNS in CNS autoimmunity while they identify potential targets for therapeutic intervention. : Araujo et al. show that neurotransmitters released by the sympathetic nervous system regulate the generation of adaptive immune responses mitigating autoimmune inflammation within the CNS. Keywords: sympathetic nervous system, experimental autoimmune encephalomyelitis, autoimmunity, β2-adrenergic receptor, ICER, GM-CSF, IFN-γ, CD4+ T cells
- Published
- 2019