Role of aryl hydrocarbon receptor (AhR) in experimental arthritis and ahr polymorphism association with rheumatoid artritis outcome

• Grant number: 10/16088-6
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2010 - October 31, 2012
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Paulo Louzada Junior
• Grantee: Paulo Louzada Junior
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Fernando de Queiroz Cunha ; Jhimmy Talbot ; Thiago Mattar Cunha

Abstract

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that affects approximately 1% of the world, and is characterized by the infiltration of immune cells in the synovial joint space. The pathogenesis of RA involves increasing the inflammatory response and Th17 immune dysfunction in regulatory T cells (Treg). Recent studies have shown that receptor activation of aryl hydrocarbon (AhR) plays a dual role in the differentiation of Treg and Th17 cells and the development of experimental encephalomyelitis, an autoimmune disease, which may reduce or exacerbate their severity. This dual modulation is dependent on the type of ligand that activates the AhR. It has also been demonstrated that activation of AhR, as well as participate in the expression of IL-17 and IL-22 in Th17 cells, also increases the expression of pro-inflammatory cytokines IL-8, IL-1beta and IL-6 in synoviocytes. In patients with RA were found high levels of expression of AhR. However, it has not been given the role of activation of this receptor in the development of both experimental arthritis and in humans. The purpose of this study is to evaluate the involvement of AhR activation in the pathogenesis of RA. To investigate the mechanisms of this effect will be used murine model of antigen-induced arthritis (AIA) and evaluated the possible association of genetic polymorphisms in the AhR with the development of RA in humans. These genetic variants in the AhR may be important prognostic markers or susceptibility to RA. (AU)