The Sympathetic Nervous System Mitigates CNS Autoimmunity via β2-Adrenergic Receptor Signaling in Immune Cells
Leandro Pires Araujo,
Juliana Terzi Maricato,
Marcia Grando Guereschi,
Maisa Carla Takenaka,
Vanessa M. Nascimento,
Filipe Menegatti de Melo,
Francisco J. Quintana,
Patrícia C. Brum,
Alexandre S. Basso
Affiliations
Leandro Pires Araujo
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil
Juliana Terzi Maricato
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil
Marcia Grando Guereschi
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil
Maisa Carla Takenaka
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil
Vanessa M. Nascimento
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil
Filipe Menegatti de Melo
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil
Francisco J. Quintana
Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02458, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Patrícia C. Brum
Escola de Educação Física e Esporte, Universidade de São Paulo, São Paulo 05508-030, Brazil
Alexandre S. Basso
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil; Corresponding author
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
