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MiR-146b-5p Decreases Cytokine Release From Astrocytes and Preserves Oligodendrocyte Progenitor Cell Complexity

Cassandra E Thompson1, Sheila Loshi1, Samantha J Carew1

  • 1Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.

The European Journal of Neuroscience
|September 5, 2025
PubMed

Insights

This study shows that increasing miR-146b-5p in astrocytes reduces inflammation and promotes oligodendrocyte progenitor cell (OPC) repair in multiple sclerosis (MS) models. This highlights miR-146b-5p as a potential therapeutic target for MS.

Area of Science:

  • Neuroimmunology
  • Cellular and Molecular Neuroscience
  • Central Nervous System (CNS) Repair

Background:

  • Multiple sclerosis (MS) is a chronic, immune-mediated CNS demyelinating disease, often relapsing-remitting.
  • Oligodendrocyte progenitor cells (OPCs) differentiate into myelinating oligodendrocytes within MS lesions, mediating repair.
  • MicroRNAs (miRNAs) are known to regulate inflammatory and repair mechanisms in MS, including OPC differentiation.

Purpose of the Study:

  • To investigate the role of miR-146b-5p in regulating astrocyte function and its impact on OPC differentiation in the context of MS.
  • To explore the molecular mechanisms by which miR-146b-5p influences astrocyte pro-inflammatory activity and OPC repair.

Main Methods:

  • Primary human and murine astrocytes were cultured, with some experiments including microglia to form mixed glial cultures.
  • miR-146b-5p levels were manipulated in astrocytes, followed by stimulation with IL-1β.
  • Measurements included IL-6 and CXCL10 production, OPC differentiation and complexity, and expression of traf6 and irak1.

Main Results:

  • Increased miR-146b-5p in astrocytes significantly reduced IL-6 and CXCL10 production upon IL-1β stimulation, an effect absent in mixed glial cultures.
  • The inhibitory effects of IL-1β on OPC differentiation and complexity were reversed by increased miR-146b-5p in astrocytes, with no effect observed in the presence of microglia.
  • Upregulation of miR-146b-5p in astrocytes led to reduced expression of traf6 and irak1, key pro-inflammatory signaling molecules.

Conclusions:

  • miR-146b-5p is an MS-relevant miRNA that modulates astrocyte function to promote OPC growth and complexity.
  • Astrocyte-specific miR-146b-5p activity is crucial for fostering CNS repair mechanisms in MS.
  • Glial-glial interactions within MS lesions significantly influence CNS injury and repair pathways, emphasizing the need for further investigation.
Keywords:
astrocytemiR‐146b‐5pmicroRNAmicrogliamultiple sclerosisoligodendrocyte progenitor cell

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