Cunha, CarolinaRomero, Paula VargasInácio, DanielPais, Ana TeresaPelicano, CatarinaCosta, MarinaMensurado, SofiaGonçalves-Sousa, NatachaPapotto, Pedro H.Neves, DanielSobral, DanielEnguita, FranciscoSilva-Santos, BrunoGomes, Anita2025-07-022025-07-022025-06Cunha C, Romero PV, Inácio D, Pais AT, Pelicano S, Gomes AQ, et al. Dissection of the microRNA transcriptomes of CD4+ T cell subsets in autoimmune inflammation identifies novel regulators of disease pathogenesis. bioRxiv. 2025 June 27.http://hdl.handle.net/10400.21/21950The authors thank Vladimir Benes and his team at the European Molecular Biology Laboratory GeneCore facility for assistance with library preparation for both the RNA and small-RNA sequencing, and the staff of the Flow Cytometry and Rodent facilities of GIMM for valuable technical assistance. This work was funded by the European Research Council (CoG_646701 to B.S.-S.) and by Fundação para a Ciência e Tecnologia (SFRH/BD/145352/2019 PhD grant to D. I.).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, and 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 miR-122-5p and miR-1247 act as peripheral brakes to CD4+ T cell pathogenicity that are subverted in the inflamed central nervous system.engAutoimmune inflammationmicroRNACD4+ T cell differentiationpreprint10.1101/2025.06.23.661017