AI Insight
Researchers used a triple reporter mouse model to profile microRNA expression in different CD4+ T cell subsets during experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. They identified 110 microRNAs differentially expressed between pro-inflammatory cells (Th1 and Th17) and anti-inflammatory regulatory T cells, discovering that miR-122-5p and miR-1247 regulate Th17 cell proliferation and Th1 cell differentiation respectively. These microRNAs appear to function as peripheral brakes on pathogenic T cell activity, but this regulatory mechanism is compromised in the inflamed central nervous system.
Why it matters
This study identifies specific microRNAs that control the balance between disease-promoting and disease-suppressing immune cells in autoimmune conditions. Understanding these regulatory mechanisms could lead to new therapeutic targets for multiple sclerosis and other autoimmune diseases by modulating microRNA activity to restore immune balance.
Understand the Science
by Carolina Cunha, Daniel Inácio, Paula Vargas Romero, Ana Teresa Pais, Catarina Pelicano, Marina Costa, Sofia Mensurado, Natacha Gonçalves-Sousa, Pedro H. Papotto, Daniel Neves, Daniel Sobral, Francisco Enguita, Bruno Silva-Santos, Anita Q. Gomes
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.