Análise da expressão de fatores de transcrição característicos de TH1, TH2, TH17 e TREG em células TCD4+ de crianças asmáticas

• Ano de defesa: 2015
• Autor(a) principal: Araújo, Patrícia Dias de
• Orientador(a): Bonorino, Cristina Beatriz C.
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul
• Programa de Pós-Graduação: Programa de Pós-Graduação em Medicina/Pediatria e Saúde da Criança
• Departamento: Faculdade de Medicina
• País: Brasil
• Palavras-chave em Português: MEDICINA; PEDIATRIA; ASMA - PREVENÇÃO E CONTROLE; LINFÓCITOS T
• Área do conhecimento CNPq: CIENCIAS DA SAUDE::MEDICINA
• Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/6252

Introduction: Asthma is a disease that affects most children, characterized by inflammation and airway hyperresponsiveness. Asthma has two main phenotypes depending on the presence of atopy. In addition to Th2 cells, Th17 cells, Th1 and Treg cells are involved in disease pathology by secreting cytokines. CD4 T cells have plasticity, which are influenced by environmental and genetic factors. Aim: To assess the phenotypic profile of CD4 T cells in asthmatic children of school age, with or without the presence of atopy and healthy controls and correlate the data with disease severity. In addition, analyze cells expressing more than one transcription factor in the blood of atopic asthmatic children to D.pteronyssinus stimulating mononuclear cells with DerP1 protein. Methods: This was a cross-sectional case-control study, where 8-14 years-old asthmatic and healthy children were recruited of public schools in Porto Alegre/RS. Mononuclear cells were isolated by Histopaque peripheral blood of children and cultured with anti-CD3/CD28 or DerP1 protein. After 24 hours the cells were stained with antibodies specific for transcription factors for analysis of Th2, Th17, Th1 and Treg cells by flow cytometry. Moreover, it was analyzed in plasma allergen-specific IgE specific. Results: The results showed that children with asthma have a higher frequency of CD4+ GATA-3+ compared to controls. Frequency of CD4+GATA-3+RORγt+ cells correlated with disease severity, except with severe therapy resistant asthma (STRA). Atopic patients showed a higher proportion of co-expressing more than one transcription factor cells compared to non-atopic individuals. Stimulation with DerP1 protein enhances the frequency of CD4 + Foxp3 +RORγt+ compared with the control and stimulation with anti-CD3/ CD28. Conclusion: In general, the results presented in this thesis allowed us to conclude that the allergens play an important role in the development of cells expressing more than one transcription factor in atopic patients. In addition, our study was the first to demonstrate that STRA children have a distinct expression profile of regulatory transcription factors of CD4 T cells Th1, Th2, Th17 and Treg compared to other severity levels of the disease.