The Mechanism of miR-223 Inhibiting Treg Differentiation in Autoimmune Encephalomyelitis by Targeting Forkhead box-O3-Forkhead box-P3 Using Nano-Albumin Particles as a Carrier

Abstract

Central nervous system (CNS) inflammatory demyelinating diseases target oligodendrocytes or supporting cells. Millions of patients worldwide suffer from a variety of symptoms including vision. Motor and sensory impairments are increasingly recognized in children, but treatments for these disorders remain very limited. This study intends to assess the mechanism of miR-223 in inhibiting regulatory T cells differentiation in autoimmune encephalomyelitis. Electron microscopy revealed nanoparticle size. miR-223 expression in tissues was detected by mRNA. MTT method and flow cytometry were used to detect Treg cell activity, proliferation and differentiation. We further studied the mechanism by which miR-223 inhibits Treg differentiation and experimental autoimmune encephalomyelitis by targeting FOXO3-FOXP3. Animal experiments were conducted on the therapeutic potential of miR-223 antagonists to confirm whether miR-223 antagonists have an effect on Experimental allergic encephalomyelitis (EAE). In our previous studies, we found that the expression of miR-223 was up-regulated in EAE and children with MOG antibody-related demyelinating diseases. Through bioinformatics analysis, we found that FOXO3 could be used as a target gene of miR-223. FOXO3 is targeted by miR-223. Using nano-albumin particles as the carrier, miR-223 mimic reduced cell activity while FOXP3 overexpression partially offset the inhibitory effect. Overexpression of FOXP3 restored the Treg induced by using nano-albumin particles as the carrier of miR-223 mimic. Our study shows that nano-albumin particles carrying miR-223 can inhibit Treg cell differentiation by targeting FOXO3. This study provides a theoretical basis for clinical research.