The role of succinate and its receptor GPR91 on the pathophysiology of experimental arthritis

• Grant number: 11/12671-1
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2011
• Effective date (End): June 30, 2015
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal researcher: José Carlos Farias Alves Filho
• Grantee: André Luis Lopes Saraiva
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that affects 1% of population and is characterized by chronic inflammation, hyperplasia of synovial tissue and infiltration of immune cells in the joint. The pathogenesis of RA involves the activation of auto-reactive T lymphocytes through the presentation of self antigens, an effect mediated by dendritic cells (DCs). Early studies show that immature DCs express the receptor GPR91, a previously orphan receptor that is part of the wide family of G protein-coupled receptors. It was also reported that succinate, a Krebs' cycle intermediate, is an endogenous ligand for GPR91 receptor. Thus, it seems that succinate, in addition to role in cellular respiration, may also play a role in the immune system. Thereby, the aim of this study is to assess the function of the succinate and GPR91 receptor on the development of rheumatoid arthritis. For this, we will evaluate: a) the contribution of succinate in triggering the specific immune response in arthritis by using experimental animal models, b) evaluate the role of succinate in the modulation of the effector response of arthritis, such as leukocyte migration and tissue injury after the onset of the disease, and c) evaluate the role of GPR91 receptors in the generation of effector responses in RA. Thus, the development of this study may lead to identification of a novel therapeutic target that driven the development of alternative drugs for the treatment of arthritis.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LUIZ, JOAO PAULO M.; TOLLER-KAWAHISA, JULIANA E.; VIACAVA, PAULA R.; NASCIMENTO, DANIELE C.; PEREIRA, PRISCILLA T.; SARAIVA, ANDRE L.; PRADO, DOUGLAS S.; LEBERT, MARC; GIURISATO, EMANUELE; TOURNIER, CATHY; CUNHA, THIAGO M.; CUNHA, FERNANDO Q.; QUESNIAUX, VALERIE; RYFFEL, BERNHARD; ALVES-FILHO, JOSE C. MEK5/ERK5 signaling mediates IL-4-induced M2 macrophage differentiation through regulation of c-Myc expression. Journal of Leukocyte Biology, AUG 2020. Web of Science Citations: 0.