Publicação

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

Detalhes bibliográficos
Resumo:	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.
Autores principais:	Cunha, Carolina
Outros Autores:	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
Assunto:	Autoimmune inflammation microRNA CD4+ T cell differentiation
Ano:	2025
País:	Portugal
Tipo de documento:	preprint
Tipo de acesso:	acesso aberto
Instituição associada:	Instituto Politécnico de Lisboa
Idioma:	inglês
Origem:	Repositório Científico do Instituto Politécnico de Lisboa

Descrição
Resumo:	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.