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Doctoral Thesis
DOI
10.11606/T.42.2011.tde-09022012-141522
Document
Author
Full name
Pedro Manoel Mendes de Moraes Vieira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Câmara, Niels Olsen Saraiva (President)
Bozza, Patricia Torres
Calich, Vera Lucia Garcia
Keller, Alexandre de Castro
Silva, João Santana da
Title in Portuguese
Leptina: um modulador central das respostas imunes.
Keywords in Portuguese
Imunologia
Imunologia de transplantes
Leptina
Transplante de pele
Abstract in Portuguese
A leptina é um mediador tanto de respostas neuroendócrinas como imunes, e tem sido associada a diversas autoimunidades. O nosso objetivo foi estudar a importância da leptina na modulação da resposta imunológica no transplante experimental, com ênfase em seu papel na plasticidade de linfócitos T e de células dendríticas (DC). Observamos que os animais deficientes em leptina têm uma sobrevida aumentada do enxerto de pele e uma menor frequência de células Th1 e maior T reguladoras (Treg), Th2 e Th17. Ademais, células T CD4+ naive diferenciam-se mais eficientemente em células Treg e Th17 tanto com DC como sem DC, na ausência de leptina. Nossos dados indicam que BMDC, imaturas e maduras, é comprometida na ausência de leptina, induzindo menor proliferação de linfócitos CD4+ e maior geração/expansão de células Treg, Th17 e Th2. Assim, a ausência de leptina resultou num predomínio de células Treg um padrão Th2 que, em conjunto com o perfil tolerogênico das DC, poderiam ser um dos mecanismos responsáveis pelo aumento da sobrevida do enxerto alogenêico de pele.
Title in English
Leptin: a central modulator of imune responses.
Keywords in English
Immunology
Leptin
Skin transplantation
Transplantation immunology
Abstract in English
Leptin is a mediator of both neuroendocrine and immune responses, and has been associated with several autoimmune diseases. Our objective was to study the importance of leptin in modulating the immune response in experimental transplantation, with emphasis on its role in the plasticity of T lymphocytes and dendritic cells (DC). We observed that animals leptin deficient had an increased skin graft survival and lower frequency of Th1 and increased regulatory (Treg), Th2 and Th17 T cells. Furthermore, naive CD4+ T cells differentiate more efficiently in Treg and Th17 cells, with DC and without DC, in the absence of leptin. Our data indicate that BMDC, mature and immature, is compromised in the absence of leptin, leading to less proliferation of CD4+ and increased generation / expansion of Treg cells, Th2 and Th17. Thus, the lack of leptin resulted in a predominance of Th2 and Treg T cells, which together with the profile of tolerogenic DC could be one of the mechanisms responsible for increased survival of allograft skin.
 
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Publishing Date
2012-03-15
 
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