Role of microRNAs in effector versus regulatory CD4+ T cell differentiation during (auto)immune responses in vivo

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 have identified miRNAs that target specific mRNAs that restrain Th17 cell proliferation and Th1 cell differentiation, impacting on the course or severity of EAE.