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Updated: Feb 5, 2026

MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
MicroRNA-183 and microRNA-96 are associated with autoimmune responses by regulating T cell activation
Jacqueline Thiel1, Christina Alter1, Sina Luppus1
1Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Germany.
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 strength of T cell activation and thereby the development and severity of T cell-dependent autoimmune diseases.
Insights
MicroRNAs (miRs) miR-183 and miR-96 enhance CD4+ T cell activation and autoimmune disease development. Inhibiting these miRs can delay autoimmune onset, suggesting therapeutic potential for T cell-mediated autoimmune conditions.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRs) are key posttranscriptional regulators of gene expression.
- miRs are implicated in modulating immune responses, including autoimmunity.
- Elevated miR-183 and miR-96 expression is observed in Graves' orbitopathy (GO) patients' CD4+ T cells.
Purpose of the Study:
- To investigate the role of miR-183 and miR-96 in T cell activation and autoimmune disease.
- To identify the targets of miR-183 and miR-96 in CD4+ T cells.
- To determine the impact of miR-183 and miR-96 on the development of T cell-dependent autoimmune diseases.
Main Methods:
- Quantification of miR-183 and miR-96 expression in CD4+ T cells from GO patients and activated human/murine T cells.
- Luciferase-based binding assays to identify miR targets.
- Retroviral gene transfer for miR overexpression and antagomiR treatment in murine CD4+ T cells.
- Assessment of EGR-1, PTEN, Akt phosphorylation, and proliferation.
- Adoptive transfer experiments in INS-HA/Rag2KO mice to evaluate autoimmune diabetes development.
Main Results:
- miR-183 and miR-96 were highly expressed in CD4+ T cells from GO patients and activated T cells.
- EGR-1 was identified as a direct target of miR-183 and miR-96.
- Overexpression of miR-183/miR-96 decreased EGR-1 and PTEN, increased Akt phosphorylation, and enhanced T cell proliferation.
- AntagomiR treatment increased EGR-1 and PTEN, and inhibited T cell proliferation.
- Adoptive transfer of miR-183/miR-96 overexpressing T cells accelerated autoimmune diabetes, while antagomiR treatment delayed it.
Conclusions:
- miR-183 and miR-96 promote T cell activation and proliferation.
- These miRs play a significant role in the development and severity of T cell-dependent autoimmune diseases.
- Targeting miR-183 and miR-96 may offer a novel therapeutic strategy for autoimmune disorders.
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