Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico

Detalhes bibliográficos
Autor(a) principal: Silva, Amanda Couto
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFRRJ
Texto Completo: https://tede.ufrrj.br/jspui/handle/jspui/5917
Resumo: 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.
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spelling Lima, D?bora Decote Ricardo de875.362.007-06http://lattes.cnpq.br/3572066508469025Lima, C?lio Freire Geraldo de002.031.157-59Lima, D?bora Decote Ricardo deSilva, Lucia Helena Pinto daBizarro, Heloisa D?Avila da Silva442.399.278-70https://orcid.org/0000-0003-1878-1696http://lattes.cnpq.br/6860723629469855Silva, Amanda Couto2022-08-23T18:28:15Z2021-09-20SILVA, Amanda Couto. Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico. 2021. 70 f. Disserta??o (Mestrado em Ci?ncias Veterin?rias) - Universidade Federal Rural do Rio de Janeiro, Serop?dica, RJ, 2021.https://tede.ufrrj.br/jspui/handle/jspui/5917Systemic 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.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: 2021-09-20CAPES - Coordena??o de Aperfei?oamento de Pessoal de N?vel Superiorapplication/pdfhttps://tede.ufrrj.br/retrieve/70439/2021%20-%20Amanda%20Couto%20Silva.pdf.jpgporUniversidade Federal Rural do Rio de JaneiroPrograma de P?s-Gradua??o em Ci?ncias Veterin?riasUFRRJBrasilInstituto de Veterin?riaAGGARWAL, R. et al. This article is protected by copyright. All rights reserved. p. 1?14, 2015. ALBERTO, C. et al. eritematoso sist?mico em cidade do Sul do Brasil. v. 51, n. 3, p. 235?239, 2011. ANDERS, H. J. et al. Lupus nephritis. Nature Reviews Disease Primers, v. 6, n. 1, 2020. ARBUCKLE, M. R. et al. Development of Autoantibodies before the Clinical Onset of Systemic Lupus Erythematosus. New England Journal of Medicine, v. 349, n. 16, p. 1526?1533, 2003. 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dc.title.por.fl_str_mv Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico
dc.title.alternative.eng.fl_str_mv Role of B1 cells in the immunopathogenesis of systemic lupus erythematosus
title Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico
spellingShingle Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico
Silva, Amanda Couto
Linf?citos B-1
L?pus eritematoso sist?mico
Imunomodula??o
Autoimunidade
B-1 lymphocytes
Systemic lupus erythematosus
Immunomodulation; autoimmunity
Medicina Veterin?ria
title_short Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico
title_full Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico
title_fullStr Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico
title_full_unstemmed Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico
title_sort Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico
author Silva, Amanda Couto
author_facet Silva, Amanda Couto
author_role author
dc.contributor.advisor1.fl_str_mv Lima, D?bora Decote Ricardo de
dc.contributor.advisor1ID.fl_str_mv 875.362.007-06
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3572066508469025
dc.contributor.advisor-co1.fl_str_mv Lima, C?lio Freire Geraldo de
dc.contributor.advisor-co1ID.fl_str_mv 002.031.157-59
dc.contributor.referee1.fl_str_mv Lima, D?bora Decote Ricardo de
dc.contributor.referee2.fl_str_mv Silva, Lucia Helena Pinto da
dc.contributor.referee3.fl_str_mv Bizarro, Heloisa D?Avila da Silva
dc.contributor.authorID.fl_str_mv 442.399.278-70
https://orcid.org/0000-0003-1878-1696
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/6860723629469855
dc.contributor.author.fl_str_mv Silva, Amanda Couto
contributor_str_mv Lima, D?bora Decote Ricardo de
Lima, C?lio Freire Geraldo de
Lima, D?bora Decote Ricardo de
Silva, Lucia Helena Pinto da
Bizarro, Heloisa D?Avila da Silva
dc.subject.por.fl_str_mv Linf?citos B-1
L?pus eritematoso sist?mico
Imunomodula??o
Autoimunidade
topic Linf?citos B-1
L?pus eritematoso sist?mico
Imunomodula??o
Autoimunidade
B-1 lymphocytes
Systemic lupus erythematosus
Immunomodulation; autoimmunity
Medicina Veterin?ria
dc.subject.eng.fl_str_mv B-1 lymphocytes
Systemic lupus erythematosus
Immunomodulation; autoimmunity
dc.subject.cnpq.fl_str_mv Medicina Veterin?ria
description 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.
publishDate 2021
dc.date.issued.fl_str_mv 2021-09-20
dc.date.accessioned.fl_str_mv 2022-08-23T18:28:15Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv SILVA, Amanda Couto. Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico. 2021. 70 f. Disserta??o (Mestrado em Ci?ncias Veterin?rias) - Universidade Federal Rural do Rio de Janeiro, Serop?dica, RJ, 2021.
dc.identifier.uri.fl_str_mv https://tede.ufrrj.br/jspui/handle/jspui/5917
identifier_str_mv SILVA, Amanda Couto. Papel dos linf?citos B-1 na imunopatog?nese do L?pus eritematoso sist?mico. 2021. 70 f. Disserta??o (Mestrado em Ci?ncias Veterin?rias) - Universidade Federal Rural do Rio de Janeiro, Serop?dica, RJ, 2021.
url https://tede.ufrrj.br/jspui/handle/jspui/5917
dc.language.iso.fl_str_mv por
language por
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