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.

Journal of Autoimmunity
|September 12, 2018
PubMed

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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