The Sympathetic Nervous System Mitigates CNS Autoimmunity via beta 2-Adrenergic Receptor Signaling in Immune Cells

Author(s)

Araujo, Leandro Pires ^{[1, 2]} ; Maricato, Juliana Terzi ^[1] ; Guereschi, Marcia Grando ^[1] ; Takenaka, Maisa Carla ^[1] ; Nascimento, Vanessa M. ^[1] ; de Melo, Filipe Menegatti ^[1] ; Quintana, Francisco J. ^{[3, 4]} ; Brum, Patricia C. ^[5] ; Basso, Alexandre S. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, BR-04023062 Sao Paulo - Brazil

^[2] Columbia Univ, Dept Microbiol & Immunol, Vagelos Coll Phys & Surg, New York, NY 10032 - USA

^[3] Harvard Med Sch, Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Boston, MA 02458 - USA

^[4] Broad Inst & Harvard, Cambridge, MA 02142 - USA

^[5] Univ Sao Paulo, Escola Educ Fis & Esporte, BR-05508030 Sao Paulo - Brazil

• Document type: Journal article
• Source: CELL REPORTS; v. 28, n. 12, p. 3120+, SEP 17 2019.
• Web of Science Citations: 1

Abstract

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). beta 2-Adrenergic receptor (Adrb2) signaling limits T cell autoimmunity in EAE through a mechanism mediated by the suppression of IL-2, IFN-gamma, 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. (AU)

• FAPESP's process: 11/02738-1 - Modulation of experimental autoimmune encephalomyelitis by the sympathetic nervous system
• Grantee: Leandro Pires Araujo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/24156-2 - Alfa2a/c adrenergic receptors-deficient mice as an animal model to study the influence of the sympathetic nervous system on the experimental autoimmune encephalomyelitis development
• Grantee: Alexandre Salgado Basso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 08/58564-9 - Study of adaptive immune response modulation by the sympathetic nervous system: emphasis on autoimmunity, Th17 cells and Foxp3 + regulatory T cells
• Grantee: Alexandre Salgado Basso
• Support Opportunities: Research Grants - Young Investigators Grants