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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2016.tde-24022016-142347
Document
Author
Full name
Marianna Mainardi Koga
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Negro, Sonia Jancar (President)
Barbuto, Jose Alexandre Marzagao
Campa, Ana
Chammas, Roger
Faccioli, Lucia Helena
Title in Portuguese
O PAF como regulador endógeno do fenótipo e função das células dendríticas.
Keywords in Portuguese
Células dendríticas
Imunização
Interleucina 10
Prostaglandina E2
Receptor do PAF
Abstract in Portuguese
Neste trabalho nós mostramos que células dendríticas (DCs) de camundongos BALB/c expressam receptor para o PAF (Fator ativador de Plaquetas) e que sua ativação promove um fenótipo tolerogênico, associado à produção de IL10 e PGE2. O bloqueio do PAF-receptor por antagonistas aumentou a capacidade das DCs induzirem proliferação de linfócitos T. O antagonista WEB2170 potencializou a resposta imune in vivo a concentração de anticorpo IgG2a OVA-específico aumentou 30 vezes no grupo tratado; a concentração de IgG1 foi semelhante nos dois grupos. O bloqueio do PAFR em camundongos imunizados com OVA em adjuvante completo de Freund, aumentou a produção de IgG1 e IgG2a OVA-específicos. Em camundongos imunizados com OVA/alum o antagonista não alterou a produção de IgG1. Estes resultados indicam que a ativação do PAFR em DCs modula a sua função apresentadora de antígenos pela produção de IL10 e PGE2. O bloqueio do PAFR pode ser útil na ativação das DCs em protocolos de vacinação com DCs e/ou como co-adjuvante em protocolos de imunização.
Title in English
PAF as an endogenous modulator of Dendritic Cells phenotype and function.
Keywords in English
Dendritic cells
Immunization
Interleukin 10
PAF receptor
Prostaglandin E2
Abstract in English
In the present work we show that BALB/c mice dendritic cells (DCs) express the PAF (platelet-activating factor) receptor and that its activation promotes a tolerogenic phenotype via IL10 and PGE2 production. Blocking PAFR by selective antagonists markedly enhanced DCs ability to induce T cell proliferation. The antagonist WEB2170 potentiated the in vivo immune response the IgG2a OVA-specific levels were 30 fold increased in the treated group; IgG1 concentration was similar for both groups. The PAFR blockade in mice immunized with OVA in complete Freunds adjuvant enhanced both IgG1 and IgG2a OVA-specific antibody production. In OVA/alum immunized mice, the antagonist did not change IgG1 production. These results suggest that PAFR activation in DCs modulates their antigen-presenting function through IL10 and PGE2 production. Blocking PAFR may be useful to induce DCs activation in DCs-based vaccination protocols and/or as a co-adjuvant in immunization protocols.
 
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Publishing Date
2016-02-24
 
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