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Activation of adrenergic receptors on macrophages and its influence on the development and course of Experimental Autoimmune Encephalomyelitis (EAE)

Grant number: 17/26242-1
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): July 01, 2018
Effective date (End): August 31, 2021
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Alexandre Salgado Basso
Grantee:Beatriz Marton Freire
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Multiple Sclerosis (MS) is an autoimmune disease characterized by the progressive loss of movements; one of its hallmarks is the demyelization of myelin sheaths that protects neurons in the Central Nervous System (CNS). The physiopathology of MS is not yet well elucidated and its treatment does not lead to cure, instead it only ameliorates the symptoms, and can also cause side effects such as immunossupression. The animal model of MS called Experimental Autoimmune Encephalomyelitis (EAE) is the best approach and most common model to study MS. This model consists in immunization of animals with the Myelin Oligodendrocyte Glycoprotein (MOG) peptide and analysis of the disease development. Normally, EAE causes ascending paralysis with loss of tonus and inflammation in the spinal cord, the progression of EAE is analyzed using a clinical score that has already been established. The main cell types involved in the development of EAE are CD4+ T lymphocytes polarized towards the Th1 and Th17 fates, auto-reactive B cells and infiltrated macrophages. Macrophage is an extremely plastic cell that can play different activities in the organism in order to maintain the homeostasis, including pro-inflammatory activities (when classically activated) and anti-inflammatory activities such as regulation of the immune response and tissue repair. Activation of macrophages depends upon the stimulus present on the microenvironment (for example, cytokines and other molecules derived from pathogens). Previous studies from our lab showed that activation of adrenergic receptors is also capable to regulate in vitro macrophage polarization. Nowadays, the influence of the nervous system on the immune system is becoming an important focus of study, in this project we are going to investigate the influence of adrenergic signaling on macrophages and how it is capable to alter the development and course of EAE. (AU)