Papel de SOCS2 no controle da inflamação e do dano articular na artrite experimental

• Ano de defesa: 2021
• Autor(a) principal: Allysson Thiago Cramer Soares
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA; Programa de Pós-Graduação em Bioquímica e Imunologia; UFMG
• Palavras-chave em Português: Artrite Reumatoide; Artrite Induzida por Antígeno; Supressor da Sinalização de Citocinas 2; Bioquímica e imunologia; Proteínas Supressoras da Sinalização de Citocina
• Link de acesso: http://hdl.handle.net/1843/77298

Rheumatoid Arthritis (RA) is a chronic joint disease that can lead to irreversible damage through the exacerbated inflammatory process in the joints, including bone and cartilage. Although current therapies have revolutionized the treatment of RA, such as immunobiological blockers of cytokine activity and intracellular signaling pathways, many patients are not responsive, in addition to presenting a high risk of infections and tumor development. Cytokine signaling suppressors (SOCS) are endogenous proteins that regulate cytokine signaling, homeostasis and pathogenesis in various diseases. However, the intersection between RA pathophysiology and SOCS2 signaling pathways is not well elucidated. In the present study, we investigated the role of SOCS2 during the development of an experimental model of antigen-induced arthritis (AIA) induced with methylated bovine serum albumin (mBSA). In wild-type (WT) mice, the co-expression of SOCS2 was reduced during the development of AIA. At the peak of inflammation, SOCS2-/- mice showed a reduced number of cells in the joint cavity. However, in the late phase of AIA, SOCS2-/- mice exhibited increased adhesion and infiltration of neutrophils, macrophages, CD4+ T cells, double positive T cells (CD4+ CD8+) and double negative T cells (CD4- CD8- ) associated with greater joint damage, loss of proteoglycans and nociception. SOCS2-/-splenocytes showed high levels of IL-17 and IFNγ after being restimulated with mBSA. Despite similar levels of lipoxin (LXA4) in WT and SOCS2- /- mice, SOCS2 deficiency resulted in fewer apoptotic neutrophils and reduced efferocytosis. Efferocytosis capacity was decreased in SOCS2-/- macrophages, and pretreatment with LXA4 did not alter efferocytic capacity when compared to WT macrophages. The present study demonstrated the vital role of SOCS2 during development and resolution during AIA. Therefore, SOCS2 could be a new therapeutic target for inflammatory joint diseases.