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Authors
Advisor(s)
Abstract(s)
O sistema imunitário é constituído por um conjunto de células com capacidade de se diferenciar, convertendo estímulos externos em complexas redes regulatórias intracelulares. Os linfócitos T CD4+ podem diferenciar se em células efetoras (Teff), entre as quais as células Th1 e Th17, que produzem as citocinas pró inflamatórias interferão γ e interleucina 17, respetivamente e em células reguladoras (Treg), que funcionam como inibidoras da ação de células Teff. Se o balanço entre as células Teff e Treg ficar comprometido, haverá um desequilíbrio na resposta imunitária que pode desencadear autoimunidade. Assim, o estudo dos mecanismos moleculares envolvidos na diferenciação destas células poderá ser crítico na prevenção da autoimunidade. Os microRNAs são RNAs não codificantes que atuam como reguladores negativos da expressão da maioria dos genes, estando envolvidos na regulação da diferenciação de células Th1, Th17 e Treg. Neste trabalho de revisão de literatura foi feita uma pesquisa sobre o perfil de expressão de microRNAs em doenças autoimunes. Foram identificados microRNAs funcionalmente importantes na regulação da expressão de genes envolvidos na diferenciação de Th1, Th17 e Treg no lúpus eritematoso sistémico, artrite reumatóide, psoríase, doença de Crohn e esclerose múltipla em modelos animais e em amostras humanas, tendo se observado que alguns miRNAs se encontram desregulados em várias doenças autoimunes. Foi também analisada a expressão dos microRNAs selecionados num modelo experimental de esclerose múltipla, tendo se identificado seis diferencialmente expressos. Conclui se que os microRNAs constituem fatores reguladores cruciais na diferenciação das células T CD4+ que poderão ser usados como potenciais biomarcadores ou como alvos terapêuticos de doenças autoimunes.
ABSTRACT - The immune system is composed of a complex network of cells with differentiating potential, which can convert external stimuli into complex intracellular regulatory networks. CD4+T lymphocytes, in particular, can differentiate into effector T cells, including Th1 and Th17 cells that produce, respectively, the pro-inflammatory cytokines interferon and interleukin 17, and regulatory T cells (Treg) that inhibit Teff action. If the balance between Teff and Treg is compromised, namely if Teff overrides Tregs, autoimmunity may arise. Thus, studying the molecular mechanisms involved in T cell differentiation might be critical to prevent autoimmunity microRNAs are non-coding RNAs that act as negative regulators of the expression of most genes and have been shown to regulate the differentiation of Th1, Th17, and Treg cells. In this literature review work, a search was made based on the expression profile of microRNAs, specifically in autoimmune diseases. Functionally important miRNAs for regulating the expression of genes involved in Th1, Th17 and Treg differentiation in systemic lupus erythematosus, rheumatoid arthritis, psoriasis, Crohn's disease, and multiple sclerosis have been identified, in both animal models and human samples. Importantly, some of the miRNAs were commonly deregualted in several autoimmune diseases. Finally, the expression of selected miRNAs was analyzed in an experimental model of multiple sclerosis, and six were differentially expressed within T cell populations. We conclude that miRNAs are crucial regulatory factors in the differentiation of CD4+ T cells that can be used as potential biomarkers or therapeutic targets of autoimmune diseases.
ABSTRACT - The immune system is composed of a complex network of cells with differentiating potential, which can convert external stimuli into complex intracellular regulatory networks. CD4+T lymphocytes, in particular, can differentiate into effector T cells, including Th1 and Th17 cells that produce, respectively, the pro-inflammatory cytokines interferon and interleukin 17, and regulatory T cells (Treg) that inhibit Teff action. If the balance between Teff and Treg is compromised, namely if Teff overrides Tregs, autoimmunity may arise. Thus, studying the molecular mechanisms involved in T cell differentiation might be critical to prevent autoimmunity microRNAs are non-coding RNAs that act as negative regulators of the expression of most genes and have been shown to regulate the differentiation of Th1, Th17, and Treg cells. In this literature review work, a search was made based on the expression profile of microRNAs, specifically in autoimmune diseases. Functionally important miRNAs for regulating the expression of genes involved in Th1, Th17 and Treg differentiation in systemic lupus erythematosus, rheumatoid arthritis, psoriasis, Crohn's disease, and multiple sclerosis have been identified, in both animal models and human samples. Importantly, some of the miRNAs were commonly deregualted in several autoimmune diseases. Finally, the expression of selected miRNAs was analyzed in an experimental model of multiple sclerosis, and six were differentially expressed within T cell populations. We conclude that miRNAs are crucial regulatory factors in the differentiation of CD4+ T cells that can be used as potential biomarkers or therapeutic targets of autoimmune diseases.
Description
Mestrado em Tecnologias Moleculares em Saúde
Keywords
Autoimunidade miRNA Células T CD4+ Treg Th1 Th17 Autoimmunity CD4+ T cells
Citation
Pinto FX. Regulação da expressão génica da diferenciação de linfócitos T CD4+ na autoimunidade [dissertation]. Lisboa: Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa; 2021.
Publisher
Instituto Politécnico de Lisboa, Escola Superior de Tecnologia da Saúde de Lisboa