MicroRNA-183 and microRNA-96 are associated with autoimmune responses by regulating T cell activation.

MicroRNA-183 and microRNA-96 are associated with autoimmune responses by regulating T cell activation. J Autoimmun. 2018 Sep 07;: Authors: Thiel J, Alter C, Luppus S, Eckstein A, Tan S, Führer D, Pastille E, Westendorf AM, Buer J, Hansen W Abstract MircoRNAs (miRs) are small molecules that regulate gene expression at the posttranscriptional level. They have been proposed to be involved in the regulation of several immune responses including autoimmunity. Here, we identified miR-183 and miR-96 to be highly expressed in CD4+ T cells from peripheral blood of Graves' orbitopathy (GO) patients as well as in human and murine T cells upon activation in vitro. By using Luciferase-based binding assays, we identified EGR-1 as target for miR-183 and miR-96. Overexpression of miR-183 and miR-96 in murine CD4+ T cells by retroviral gene transfer resulted in decreased EGR-1 and PTEN expression, elevated Akt phosphorylation and enhanced proliferation. In contrast, treatment of murine CD4+ T cells with specific antagomiRs increased EGR-1 and PTEN expression and interfered with the proliferative activity upon stimulation in vitro. Strikingly, adoptive transfer of miR-183 and miR-96 overexpressing antigen-specific T cells into INS-HA/Rag2KO mice accelerated the development of autoimmune diabetes, whereas transfer of antagomiR-treated cells delayed the disease onset. These results indicate that miR-183 and miR-96 have the ability to regulate the stren...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research