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MicroRNA-92a Drives Th1 Responses in the Experimental Autoimmune Encephalomyelitis

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Abstract

Dysregulation of microRNAs (miRNAs) has been linked to the progress of a number of autoimmune diseases including multiple sclerosis (MS), and its animal model, experimental autoimmune encephalomyelitis (EAE). IFN-γ-producing Th1 cells are major players in MS/EAE pathogenesis. It is known that differentiation of T cells towards the Th1 phenotype is influenced by various factors including miRNAs. The miR-92a shows substantial upregulation in MS; however, little is known about its role in the development of autoimmune and inflammatory responses. Herein, we investigated the role of miR-92a in the pathogenesis of MS, focusing on its potential effects on differentiation of Th1 cells. The expression levels of miR-92a were assessed in the spinal cord tissues and splenocytes from mice with EAE using real-time RT-PCR. Next, using transfection with miR-92a mimic sequences, the potential involvement of miR-92a in Th1 polarization was investigated by flow cytometric analysis. Moreover, the expression levels of miR-92a targets were explored in spinal cord tissues of EAE mice. miR-92a expression was enhanced in mouse spinal cord samples at the peak of EAE disease. Overexpression of miR-92a in splenocytes led to increased differentiation of Th1 cells compared with cells transfected with negative control sequences. Enhanced miR-92a expression was accompanied by reduced expression TSC1 or DUSP10, predicted miR-92a targets, in EAE spinal cords. Our data point to a potential role for miR-92a in neuroinflammatory responses in EAE. Our results indicate that miR-92a might affect Th1 differentiation, likely due to downregulation of TSC1 and DUSP10

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Authors and Affiliations

  1. Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Nahid Rezaei, Abbas Rezaei & Mazdak Ganjalikhani Hakemi

  2. Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Farideh Talebi, Samira Ghorbani & Farshid Noorbakhsh

  3. Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

    Abolghasem Esmaeili

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  1. Nahid Rezaei
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  2. Farideh Talebi
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  4. Abbas Rezaei
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Correspondence to Farshid Noorbakhsh or Mazdak Ganjalikhani Hakemi.

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All experiments were performed in accordance with guidelines of the Research Ethics Committee of Isfahan University of Medical Sciences.

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The authors declare that they have no conflict of interest.

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All experiments were performed in accordance with guidelines of the Research Ethics Committee of Isfahan University of Medical Sciences (Code of Ethics: IR.MUI.REC.1394.3.134).

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Rezaei, N., Talebi, F., Ghorbani, S. et al. MicroRNA-92a Drives Th1 Responses in the Experimental Autoimmune Encephalomyelitis. Inflammation 42, 235–245 (2019). https://doi.org/10.1007/s10753-018-0887-3

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