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Estudo da resposta Th17 no transplante renal alog?nico: contribui??o do eixo quimiot?tico CCR6/CCL20 e dos polimorfismos g?nicos em IL17A e IL17RA / Th17 response in allogeneic renal transplantation: contribution of CCR6/CCL20 axis and genetic polymorphisms in IL17A and IL17RA

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Previous issue date: 2015-04-24 / O transplante renal ? a melhor forma de tratamento para indiv?duos que perderam a fun??o do
rim. Pacientes transplantados renais necessitam de rigoroso esquema imunossupressor para
evitar rejei??o. Nesse processo c?lulas T helper do sistema imunol?gico exercem papel chave
na resposta contra o enxerto, sendo as c?lulas Th17 recentemente investigadas por produzirem
IL-17, uma potente citocina pr?-inflamat?ria cujo papel na rejei??o tamb?m vem sendo
descrito. O aumento da express?o de c?lulas Th17 tem importante associa??o ao
desenvolvimento da rejei??o no microambiente renal, no entanto o prov?vel mecanismo ainda
n?o est? bem compreendido. Esse estudo teve como objetivo avaliar a resposta Th17 a partir
da influ?ncia exercida pelo eixo quimiot?tico CCR6/CCL20 e por variantes gen?ticas na IL- 17 e seu receptor IL-17RA. Para isso, realizou-se um estudo caso controle envolvendo 148
pacientes transplantados do Hospital Universit?rio Onofre Lopes/UFRN no qual se avaliou
por imunohistoqu?mica a express?o proteica da IL-17 e das quimiocinas CCR6/CCL20 e por
PCR-RFLP as variantes gen?ticas em IL17A e IL17RA. Nossos resultados demonstraram n?o
haver influ?ncia dos polimorfismos g?nicos sobre o desfecho do enxerto ou sobre a express?o
proteica da IL-17. No microambiente do enxerto renal encontramos v?rias fontes produtoras
de IL-17: c?lulas epiteliais tubulares, c?lulas glomerulares, neutr?filos e c?lulas do infiltrado
intersticial, por sua vez a express?o do eixo quimiot?tico CCR6/CCL20 ficou restrita a c?lulas
do epit?lio tubular. Houve uma leve correla??o linear positiva entre a presen?a de IL-17 e a
express?o do eixo quimiot?tico CCR6/CCL20 no microambiente do enxerto renal.
Acreditamos que, aliado aos nossos resultados, estudos posteriores com aumento do ?n?
amostral e um maior controle sobre as vari?veis que envolvem a obten??o do esp?cime renal,
podem determinar com maior clareza a influ?ncia exercida pelo eixo quimiot?tico
CCR6/CCL20 e a exercida por polimorfismos gen?ticos em citocinas, sobre o controle da
resposta Th17 nos processos de rejei??o ao aloenxerto renal. / Kidney transplantation is the best treatment for patients who have lost kidney function. Renal
transplant patients require accurate immunosuppressive drugs to prevent rejection. In this
process T helper cells of the immune system perform key role in the immune response to the
graft, and recently the Th17 cells has been investigated by production of IL-17 potent
proinflammatory cytokine whose role in the rejection has also been described. Increased of
Th17 cell expression has an important association with the development of rejection in renal
microenvironment, however the likely mechanism is not well understood. This study aimed to
evaluate the Th17 response from the influence of the chemotactic axis CCR6/CCL20 and
genetic variants in IL-17 and IL-17RA. We conducted a case-control study involving 148
patients transplanted at the University Hospital Onofre Lopes/UFRN in which assessed by
immunohistochemistry protein expression of IL-17 and chemokines CCR6/CCL20 and by
PCR-RFLP genetic variants in IL17A and IL17RA. Our results showed no influence of genetic
polymorphisms on the outcome of the graft or the protein expression of IL-17. In renal graft
microenvironment found several sources producing IL-17: tubular epithelial cells, glomerular
cells, neutrophils and cell interstitial infiltration, in turn the expression of chemotactic axis
CCR6/CCL20 was restricted to the tubular epithelium cells. There was a slight positive linear
correlation between the presence of IL-17 and expression of chemotactic axis CCR6/CCL20
in the microenvironment of renal graft. Therefore, we believe that, combined with our results,
further studies with increased "n" sample and greater control over the variables involved in
obtaining the renal specimen, can determine more clearly the influence of chemotactic axis
CCR6 / CCL20 and polymorphisms in cytokines related to Th17 profile on the control of this
cell subtype response in rejection processes to renal allograft.

Identiferoai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/20041
Date24 April 2015
CreatorsLima, Antonnyo Palmielly Di?genes
Contributors91430364491, http://lattes.cnpq.br/2644540835478572, Jatob?, Carlos Andr? Nunes, 67567045400, http://lattes.cnpq.br/8755924262557104, Silva, Norma Lucena Cavalcanti Licinio da, 32591187487, http://lattes.cnpq.br/7341938714365067, Genre, Julieta, Freitas, Janaina Cristiana de Oliveira Crispim
PublisherUniversidade Federal do Rio Grande do Norte, PROGRAMA DE P?S-GRADUA??O EM CI?NCIAS FARMACEUTICAS, UFRN, Brasil
Source SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis
Sourcereponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN
Rightsinfo:eu-repo/semantics/openAccess

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