Myocardial Gene Expression of T-bet, GATA-3, Ror-gamma t, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed T(H)1-Type Response

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art_NOGUEIRA_Myocardial_Gene_Expression_of_Tbet_GATA3_Rorgamma_t_2014.PDF (1.47 MB)
Citações na Scopus
52
Tipo de produção
article
Data de publicação
2014
DOI
Scopus
Web of Science
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Título do Volume
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HINDAWI PUBLISHING CORPORATION
Autores
Citação
MEDIATORS OF INFLAMMATION, article ID 914326, 9p, 2014
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
Background. Chronic Chagas disease cardiomyopathy (CCC), a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC). Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (T(H)1/T(H)2/T(H)17/Treg) in CCC, NIC, and heart donor myocardial samples. Methods and Results. Quantitative PCR showed markedly upregulated expression of IFN-gamma and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by T(H)2 cells (IL-4, IL-5, and IL-13) or associated with Treg (TGF-beta and IL-10) were not upregulated in CCC myocardium. Expression of T(H)1-related genes such as T-bet, IFN-gamma, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. Conclusions. Results are consistent with a strong local T(H)1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3(+)CTLA4(+) Treg cell population, which is unable to completely curb IFN-gamma production in CCC myocardium, therefore fueling inflammation.
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https://observatorio.fm.usp.br/handle/OPI/8381
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/11
Artigos e Materiais de Revistas Científicas - LIM/19