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Characterisation of miR-34c-5p’s role in human and mouse T cell function
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Resumo(s)
CD4+ T cells are the central orchestrators of immune responses. They play a critical role not only in phagocytic-mediated clearance of pathogens and stimulation of B cells, promoting antibody production, but also in regulating unwanted immune activation. After encountering an antigen, CD4+ T cells undergo activation and differentiation into specific subsets, T helper (Th) cells and regulatory T (Treg) cells, depending on the nature of the cytokines present at the activation site. miRNAs are small regulatory non-coding RNAs, capable of fine-tuning gene expression, with well-established roles in the immune system, such as in immune cell differentiation and immune responses to viral infections. Recently, miR-34c-5p was identified as being transcriptionally activated in response to TCR stimulation in human naïve CD4+ T cell, suggesting it is a novel regulator of T cell function. Since the regulatory mechanisms behind the expression of miR-34c-5p in human CD4+ T cells are poorly understood, we studied the regulation of candidate promoter regions of this miRNA, in vitro, to identify TFs, crucial in this process. Results indicate c-Myc, p53 and Fos as positive regulators of promoter C. We also aimed to map the transcription start site of miR-34c-5p primary transcript in naïve CD4+ T cells, upon TCR stimulation, with preliminary results directing the focus on promoter B. In contrast with previous results, we were able to detect the expression of this miRNA in memory CD4+ T cells. Preliminary studies to assess if the expression pattern of this miRNA in humans is observed in mouse, demonstrate that miR-34c-5p is expressed in mouse Th0 cells, 96h post-TCR stimulation. Overall, our results identified positive regulators for promoter C and provided new insights regarding the primary transcript in TCR-activated naïve CD4+ cells, directing future work for the thorough characterization of promoter B.
Descrição
Tese de mestrado, Bioquímica (Bioquímica Médica), Universidade de Lisboa, Faculdade de Ciências, 2021
Palavras-chave
microRNAs regulação da expressão de miRNAs miR-34c-5p sistema imunitário ativação de células T Teses de mestrado - 2021