MicroRNAs -122 and -1247 restrain the pathogenicity of effector CD4+ T cells in autoimmune inflammation

Abstract A hallmark of autoimmune diseases like multiple sclerosis (MS) is an imbalance between CD4+ T cell subsets, namely pro-inflammatory T helper 1 (Th)1 and Th17 cells, and anti-inflammatory Foxp3+ regulatory cells (Treg). Here we investigated which and how microRNAs (miRNAs) regulate these CD4+ T cell subsets in a pre-clinical model of MS. We established a triple reporter mouse for Ifng, Il17 and Foxp3, subjected it to experimental autoimmune encephalomyelitis (EAE), and identified the miRNomes of purified Th1, Th17 and Treg cells. We found that miR-122-5p and miR-1247 target specific sets of mRNAs to restrain Th17 cell proliferation and Th1 cell differentiation, respectively, thus impacting on the course or severity of EAE. Cytokine-regulated miR-122-5p and miR-1247 expression levels inversely associated with pathogenic gene signatures between lymphoid and central nervous systems, indicating that these miRNAs act as peripheral brakes to CD4+ T cell pathogenicity that are subverted in the inflamed target organ.