Malat1 long noncoding RNA regulates inflammation and leukocyte differentiation in experimental autoimmune encephalomyelitis.

ABSTRACT

In this study, we investigated the contributions of the MALAT1 long noncoding RNA to autoimmune neuroinflammation in central nervous system tissues from patients with multiple sclerosis (MS) and mice with experimental autoimmune encephalomyelitis (EAE). Expression of MALAT1 was decreased in the spinal cords of EAE mice as well as in stimulated splenocytes and primary macrophages. MALAT1 downregulation by specific siRNAs enhanced the polarization of macrophages towards the M1 phenotype. Interestingly, siRNA-mediated MALAT1 downregulation shifted the pattern of T-cell differentiation towards a Th1/Th17 cell profile and decreased differentiation towards a Tregs phenotype. Proliferation of T-cells was also increased following MALAT1 downregulation. These data point to a potential anti-inflammatory effect for MALAT1 in the context of autoimmune neuroinflammation.