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Publication
MicroRNA determinants of the balance between effector and regulatory CD4+ T cells in vivo
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Advisor(s)
Abstract(s)
MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that control gene expression at the post-transcriptional level. As in many physiological processes, they have been implicated in the regulation of the immune system, including the differentiation and function of CD4+ T cell subsets. CD4+ T cells are key players in host defense against pathogens, but an incorrect balance between different CD4+ T cell subsets, namely pro-inflammatory effector T cells, including the IFN-γ-producers T helper 1 (Th)1 and the IL-17-producers Th17 cells, and anti-inflammatory regulatory T cells (Treg; FoxP3+ subset), can lead to immune-mediated diseases. We believe that a holistic approach based on in vivo models is required to understand how miRNA networks may control the balance between effector and regulatory subsets under physiological conditions. To address this, we have established a triple reporter mouse for Ifng (Th1 subset), Il17 (Th17 subset), and Foxp3 (Treg subset), and subject it to experimental autoimmune encephalomyelitis (EAE). We have then performed miRNA-seq in Th1, Th17 and Treg cells isolated from the spleen and lymph nodes of these mice at the peak-plateau stage. Our data indicate that 110 miRNAs are differentially expressed between effector and regulatory subsets in vivo. From these, we selected 10 miRNA candidates that were specifically upregulated in one of the T cell subsets when compared with the others. To understand the functional impact of miRNA candidates in T cell differentiation in vitro, we first assessed the miRNA expression profile of naïve CD4+ T cells cultured under Th1, Th17 and Treg polarizing conditions. Data demonstrated that five miRNAs recapitulated the in vivo expression pattern. We will further determine the role of the miRNA candidates in T cell subsets differentiation using gain- and loss-of-function strategies, as well as establish the miRNA-target networks that may impact effector/regulatory T cell balance in vivo.
Description
Keywords
Immune system MicroRNA CD4+ T cells in vivo
Citation
Cunha C, Romero PV, Pelicano C, Papotto P, Schmolka N, Gomes AQ, et al. MicroRNA determinants of the balance between effector and regulatory CD4+ T cells in vivo. In: RNA Regulatory Network, 3rd International Symposium on Frontiers in Molecular Science, Pavilhão do Conhecimento, Lisbon (Portugal), June 26-28, 2019.