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Updated: Dec 7, 2025
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Published on: August 4, 2022
Mir106b-25 and Mir17-92 Are Crucially Involved in the Development of Experimental Neuroinflammation
Annamaria Finardi1, Martina Diceglie1, Luca Carbone1
1Clinical Neuroimmunology Unit, Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Abstract:
MicroRNAs (miRNAs) are single-stranded RNA that have key roles in the development of the immune system and are involved in the pathogenesis of various autoimmune diseases. We previously demonstrated that two members of the miR106b-25 cluster and the miR17-92 paralog cluster were upregulated in T regulatory cells from multiple sclerosis (MS) patients. The aim of the present work was to clarify the impact of miR106b-25 and miR17-92 clusters in MS pathogenesis. Here, we show that the mice lacking miR17-92 specifically in CD4+ T cells or both total miR106b-25 and miR17-92 in CD4+ T cells (double knockout) are protected from Experimental Autoimmune Encephalomyelitis (EAE) development while depletion of miR106b-25 only does not influence EAE susceptibility. We suggest that the absence of miR106b does not protect mice because of a mechanism of compensation of miR17-92 clusters. Moreover, the decrease of neuroinflammation was found to be associated with a significant downregulation of pro-inflammatory cytokines (GM-CSF, IFNγ, and IL-17) in the spinal cord of double knockout EAE mice and a reduction of Th17 inflammatory cells. These results elucidate the effect of miR106b-25 and miR17-92 deletion in MS pathogenesis and suggest that their targeted inhibition may have therapeutic effect on disease course.
Insights
MicroRNAs (miRNAs) play a role in multiple sclerosis (MS). Deleting miR17-92 or both miR106b-25 and miR17-92 in CD4+ T cells protected mice from experimental autoimmune encephalomyelitis (EAE), suggesting therapeutic potential.
Area of Science:
- Immunology
- Molecular Biology
- Neuroscience
Background:
- MicroRNAs (miRNAs) are crucial regulators of immune system development and are implicated in autoimmune disease pathogenesis.
- Previous studies identified upregulation of miR106b-25 and miR17-92 clusters in T regulatory cells of multiple sclerosis (MS) patients.
Purpose of the Study:
- To investigate the specific roles of the miR106b-25 and miR17-92 miRNA clusters in the pathogenesis of multiple sclerosis.
- To determine the impact of deleting these miRNA clusters in CD4+ T cells on disease development and neuroinflammation.
Main Methods:
- Generation of genetically modified mice lacking specific miRNA clusters (miR17-92 or both miR106b-25 and miR17-92) in CD4+ T cells.
- Induction of Experimental Autoimmune Encephalomyelitis (EAE), a mouse model for MS.
- Assessment of EAE development, neuroinflammation, pro-inflammatory cytokine levels (GM-CSF, IFNγ, IL-17), and Th17 cell populations in the spinal cord.
Main Results:
- Mice lacking miR17-92 specifically in CD4+ T cells, or both miR106b-25 and miR17-92 clusters (double knockout), were protected from EAE development.
- Depletion of only the miR106b-25 cluster did not affect EAE susceptibility, suggesting compensatory mechanisms by the miR17-92 cluster.
- Double knockout mice exhibited decreased neuroinflammation, characterized by downregulation of pro-inflammatory cytokines and a reduction in Th17 cells.
Conclusions:
- The miR106b-25 and miR17-92 miRNA clusters play a significant role in the pathogenesis of multiple sclerosis.
- Targeted inhibition of these miRNA clusters, particularly miR17-92, may represent a potential therapeutic strategy for managing MS disease course.
- CD4+ T cell-specific deletion of miR17-92 is sufficient to confer protection against EAE, highlighting the importance of these miRNAs in T cell-mediated autoimmunity.
