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Doctoral Thesis
DOI
10.11606/T.42.2018.tde-16022018-120240
Document
Author
Full name
Marina Burgos da Silva
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Câmara, Niels Olsen Saraiva (President)
Cavinato, Regiane Aparecida
Kerbauy, Daniella Marcia Bahia
Ortis, Fernanda
Starobinas, Nancy
Title in Portuguese
Papel da obesidade na rejeição de transplantes alogênicos.
Keywords in Portuguese
Inflamação
Obesidade
Rejeição de enxerto
Transplante de medula óssea
Transplante de pele
Abstract in Portuguese
Além de modular o metabolismo energético, o tecido adiposo constitui um regulador endócrino, produzindo fatores como a adiponectina (APN), adipocina pouco expressa na obesidade, com propriedades imunoreguladoras. Neste trabalho investigamos o papel da obesidade e APN em modelos murinho de transplante de pele e doença do enxerto-versus-hospedeiro (GvHD), na obesidade induzida por dieta hiperlipídica (Ob) e animais knockout (KO) para APN. Em suma, receptores Ob e APN KO apresentaram rejeição acelerada de enxerto de pele, associado inflamação do tipo Th1 e Th17. A obesidade também levou a pior GvHD, associado a maior inflamação no fígado, pulmão, intestino junto a dano hepático e intestinal, enquanto a manutenção de dieta HF após o transplante preveniu parciamente este dano. Estudos in vitro corroboraram estes resultados, mostrando maior ativação dendrítica e linfocitária em meio mimetizando a obesidade. Desta forma, este estudo sugere que a obesidade e redução de APN levam a maior rejeição de transplantes sugerindo adiante um papel importante à dieta neste processo.
Title in English
Role of obesity in alogeneic transplant rejection.
Keywords in English
Bone marrow transplant
Graft rejection
Inflammation
Obesity
Skin transplant
Abstract in English
In addition to modulating energy metabolism, the adipose tissue is an endocrine regulator, producing factors such as adiponectin (APN), an adipokine little in obesity, with immunoregulatory properties. In this work we investigated the role of obesity and APN in skin transplant and graft-versus-host disease (GvHD) in high-fat diet induced obesity (Ob) and knockout (KO) mice for APN. In summary, Ob and APN KO receptors showed accelerated skin graft rejection, associated with Th1 and Th17 type inflammation. Obesity also led to worse GvHD, associated with increased inflammation in liver, lung, intestines along with liver and gut damage, while maintenance of the HF diet after transplantation partially prevented this damage. In vitro studies corroborated these results, showing greater dendritic and lymphocytic activation in conditions mimicking obesity. Thus, this study suggests that obesity and reduced APN lead to greater rejection of transplants further suggesting an important role of diet in this process.
 
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Release Date
2020-02-16
Publishing Date
2018-02-16
 
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