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Master's Dissertation
DOI
10.11606/D.10.2013.tde-07012014-083924
Document
Author
Full name
Daniel Sanzio Gimenes da Cruz
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Gomes, Cristina de Oliveira Massoco Salles (President)
Barbuto, Jose Alexandre Marzagao
Pinto, Frederico Azevedo da Costa
Title in Portuguese
Caracterização fenotípica e funcional de células dendríticas após vagotomia unilateral cervical em camundongos C57BL/6
Keywords in Portuguese
células dendríticas
nervo vago
neuroimunomodulação
Abstract in Portuguese
O nervo vago exerce um papel importante na regulação da homeostase, e seus ramos eferentes emitem sinais capazes de atenuar a resposta inflamatória através da via do reflexo inflamatório. Nossa hipótese foi de que esta via pode também alterar a função das células dendríticas (DCs), uma vez que estas células possuem receptores colinérgicos e podem ser reguladas pelas citocinas inflamatórias. Sendo assim, DCs esplênicas e DCs geradas a partir de células precursoras da medula óssea de animais vagotomizados unilateralmente foram analisadas quanto aos marcadores fenotípicos CD11c e MHC-II e as moléculas co-estimuladoras CD80 e CD86. As DCs derivadas da medula óssea ainda foram avaliadas quanto a função fagocítica, a apresentação de antígenos, bem como, a produção de citocinas do cocultivo destas com linfócitos de camundongos OT-II. Um ensaio de reação de hiperensibilidade tardia (DTH) para se avaliar a resposta imune celular também foi realizado, mas não mostrou alterações significantes. A análise dos marcadores fenotípicos revelou um aumento da expressão de CD80 em DCs esplênicas de animais vagotomizados unilateralmente, mas não houveram alterações nas DCs derivadas da medula óssea. A avaliação da capacidade fagocítica revelou uma diminuição significante em DCs derivadas da medula óssea de animais vagotomizados unilateralmente enquanto no ensaio de proliferação de linfócitos OTII não houve efeito significante. Entre as citocinas avaliadas, a IL-6 e IFN-ϒ se apresentaram aumentadas nos animais vagotomizados unilateralmente. Portanto, o presente trabalho foi capaz de evidenciar que as DCs também estão sujeitas à modulação do sistema nervoso parassimpático, e que, uma vez moduladas, estas células são capazes de exercer influências sobre outras células do sistema imunológico.
Title in English
Phenotypic and functional characterization of dendritic cells following unilateral cervical vagotomy in C57BL/6 mice
Keywords in English
dendritic cells
neuroimmunomodulation
vagus nerve
Abstract in English
The vagus nerve plays an important role in the regulation of homeostasis and its efferent branches emit signals capable of attenuating the inflammatory response via the inflammatory reflex. Our hypothesis was that this pathway may also alter the function of dendritic cells (DCs), since these cells have cholinergic receptors and can be regulated by the inflammatory cytokines. Thus, splenic DCs and DCs generated from bone marrow precursor cells unilaterally vagotomized animals were analyzed for phenotypic markers CD11c and MHC-II and co-stimulatory molecules CD80 and CD86. The bone marrow-derived DCs were also evaluated for phagocytic function, antigen presentation, as well as the production of cytokines such co-culture with lymphocytes from mice OT-II. A delayed type hypersensitivity test (DTH) twas also performed to evaluate the cellular immune response was also performed, but showed no significant changes. The analysis of phenotypic markers showed increased CD80 expression in splenic DCs from unilaterally vagotomized animals but there were no changes in bone marrow-derived DCs. The evaluation of phagocytic ability showed a significant decrease in DCs from unilaterally vagotomized animals while in the OT-II lymphocyte proliferation assay there was no significant effect. Among the cytokines evaluated, IL-6 and IFN-ϒ were increased in unilaterally vagotomized animals. Therefore, this study was able to demonstrate that DCs are also subject to modulation of the parasympathetic nervous system, which, once modulated, these cells are able to exert influence on other cells.
 
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Publishing Date
2014-08-13
 
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