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A microRNA atlas of CD4+ T cell subsets in experimental autoimmune encephalomyelitis identifies regulators of disease pathogenesis

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Resumo(s)

MicroRNAs (miRNAs) are key regulators of CD4+ T cell differentiation, but how they contribute to the course of an autoimmune disease in vivo remains poorly studied. Given the known roles in autoimmunity of pro-inflammatory T helper 1 (Th)1 and Th17 cells, and anti-inflammatory Foxp3+ regulatory cells, we established a triple-reporter mouse for Ifng, Il17, and Foxp3. We subjected it to experimental autoimmune encephalomyelitis (EAE) to characterize the miRNomes of the corresponding CD4+ T cell subsets. We identified 110 miRNAs differentially expressed between the pro-inflammatory (Th1 and Th17 cells) and the Treg cell subsets. Among these, we found novel functions for miR-122-5p and miR-1247 as regulators of Th17 cell proliferation and Th1 cell differentiation, thus impacting the course or severity of EAE, respectively. Importantly, their expression patterns suggest that miR-122-5p and miR-1247 act as peripheral brakes on CD4+ T cell pathogenicity that are subverted in the inflamed central nervous system.

Descrição

CD4+ T cell RNA-seq data are available from the Sequence Read Archive (SRA) under the accession code PRJNA1067547 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1067547). The raw flow cytometry data (FCS files) have been deposited in Zenodo and are available at https://doi.org/10.5281/zenodo.21341947. All other data that support the findings of this study are available in the article and Supplementary Information.
This work was funded by the European Research Council, by “la Caixa” Foundation, and by Fundação para a Ciência e Tecnologia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Palavras-chave

Encephalomyelitis CD4+ T cell subsets microRNA atlas

Contexto Educativo

Citação

Cunha C, Inácio D, Romero PV, Pais AT, Pelicano C, Gomes AQ, et al. A microRNA atlas of CD4+ T cell subsets in experimental autoimmune encephalomyelitis identifies regulators of disease pathogenesis. PLoS Biol. 2026;24(8):e3003271.

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Public Library of Science (PLoS)

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