Dissection of the microRNA transcriptomes of CD4+ T cell subsets in autoimmune inflammation identifies novel regulators of disease pathogenesis

Cunha, Carolina; Romero, Paula Vargas; Inácio, Daniel; Pais, Ana Teresa; Pelicano, Catarina; Costa, Marina; Mensurado, Sofia; Gonçalves-Sousa, Natacha; Papotto, Pedro H.; Neves, Daniel; Sobral, Daniel; Enguita, Francisco; Silva-Santos, Bruno; Gomes, Anita

http://hdl.handle.net/10400.21/21950

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Authors

Gonçalves-Sousa, Natacha

Papotto, Pedro H.

Neves, Daniel

Abstract(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, 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.

Description

The 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.).

Keywords

Autoimmune inflammation microRNA CD4+ T cell differentiation

URI

http://hdl.handle.net/10400.21/21950

Citation

Cunha 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.