Role of B1 cells in the immunopathogenesis of systemic lupus erythematosus

Autor: Silva, Amanda Couto
Přispěvatelé: Lima, D?bora Decote Ricardo de, Lima, C?lio Freire Geraldo de, Silva, Lucia Helena Pinto da, Bizarro, Heloisa D?Avila da Silva
Jazyk: portugalština
Rok vydání: 2021
Předmět:
Zdroj: Biblioteca Digital de Teses e Dissertações da UFRRJ
Universidade Federal Rural do Rio de Janeiro (UFRRJ)
instacron:UFRRJ
Popis: Submitted by Jorge Silva (jorgelmsilva@ufrrj.br) on 2022-08-23T18:28:15Z No. of bitstreams: 1 2021 - Amanda Couto Silva.pdf: 6176891 bytes, checksum: e6a055b3b998e552f2a73e44fe35ea72 (MD5) Made available in DSpace on 2022-08-23T18:28:15Z (GMT). No. of bitstreams: 1 2021 - Amanda Couto Silva.pdf: 6176891 bytes, checksum: e6a055b3b998e552f2a73e44fe35ea72 (MD5) Previous issue date: 2021-09-20 CAPES - Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects dogs, cats, horses, humans and primates. The pathogenesis is multifactorial, being associated with genetic, hormonal and environmental factors. SLE leads to deposition of immune complexes in joints and various organs, resulting in clinical manifestations. The participation of T and B lymphocytes is crucial for the pathogenesis of the disease. B-1 lymphocytes, a subpopulation of B cells, have characteristics that may contribute to the pathogenesis of autoimmune diseases through the secretion of cytokines such as IL-10 exerting a modulating action on both the acute and chronic inflammatory response, presenting antigens to T cells, participating of innate and adaptive immunity and are the main producers of natural antibodies. Understanding the role of B-1 cells in SLE immunopathogenesis may open new fronts for studies on immunotherapeutic strategies to control this complex and multifactorial disease. The present work evaluated the role of B-1 cells in the immunopathogenesis of SLE using the pristane induction model. SLE was induced in BALB/c, XID (B-1 deficient) and XID mice repopulated with B-1. The animals were evaluated for six months. We found that BALB/c pristane and XID repopulated with B-1 showed characteristic signs of the disease, such as lipogranuloma formation and splenomegaly. Notably, BALB/c pristane also presented ascites, joint edema, arthritis, kidney damage with immune complex deposition. In the spleen, animals BALB/c had a higher percentage of B cells (CD19+, IgM+), BALB/c pristane T CD8 (CD3+, CD8+), while XID pristane had increased T CD4 (CD3+,CD4+). In the peritoneal lavage, after induction with pristane, there was a decrease in B cells (CD19+, IgM+) and an increase in B1a (CD19+, IgM CD5+) in BALB/c pristane. In peripheral blood, BALB/c had a higher number of lymphocytes, XID had a neutrophilic profile, and all groups with SLE showed an increase in monocytes. The cytokines IL-10, IL-6 and IFN-? were increased in BALB/c and XID repopulated that developed SLE. Based on these results, we suggest that the presence of B-1 cells may contribute to the development of SLE. O L?pus eritematoso sist?mico (LES) ? uma doen?a autoimune cr?nica que acomete c?es, gatos, cavalos, humanos e primatas. A patog?nese ? multifatorial, estando associado a fatores gen?ticos, hormonais e ambientais. O LES leva a deposi??o de complexos imunes em articula??es e diversos ?rg?os resultando em manifesta??es cl?nicas. A participa??o dos linf?citos T e B ? crucial para a patog?nese da doen?a. Linf?citos B-1, uma subpopula??o de c?lulas B, possuem caracter?sticas que podem contribuir com a patog?nese de doen?as autoimunes pois s?o capazes de secretar citocinas como IL-10 exercendo uma a??o moduladora tanto da resposta inflamat?ria aguda como cr?nica, apresentam ant?genos as c?lulas T, participam da imunidade inata e adaptativa e s?o as principais produtoras de anticorpos naturais. O entendimento do papel das c?lulas B-1 na imunopatog?nese do LES pode abrir frentes de estudos sobre estrat?gias de imunoterapias que possibilitem o controle dessa doen?a complexa e multifatorial. O presente trabalho avaliou o papel das c?lulas B-1 na imunopatog?nese do LES utilizando o modelo de indu??o pelo pristane. LES foi induzido em camundongos f?meas BALB/c, XID (deficientes em B-1) e XID repopulados com B-1. Os animais foram avaliados por seis meses. Verificamos que, BALB/c pristane e XID repopulados com B-1 apresentaram sinais caracter?sticos da doen?a como, forma??o de lipogranulomas e esplenomegalia. Em destaque, BALB/c pristane tamb?m apresentou ascite, edema articular, artrite, les?o renal com deposi??o de imunocomplexo. No ba?o, os animais BALB/c tiveram maior porcentagem de c?lulas B (CD19+, IgM+), BALB/c pristane de T CD8 (CD3+,CD8+), enquanto XID pristane teve aumento T CD4 (CD3+,CD4+). No lavado peritoneal, ap?s indu??o com pristane houve diminui??o de c?lulas B (CD19+, IgM+) e aumento de B1a (CD19+ IgM+ CD5+) em BALB/c pristane. No sangue perif?rico, BALB/c apresentou maior quantidade de linf?citos, XID apresentou um perfil neutrofilico, e em todos os grupos com LES houve aumento de mon?citos. As citocinas IL-10, IL-6 e IFN-? foram aumentadas nos BALB/c e XID repopulados. Com base nesses resultados, sugerimos que a presen?a de c?lulas B-1 pode contribuir com o desenvolvimento do LES.
Databáze: OpenAIRE
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