Interleukin-17A stimulation induces alterations in Microglial microRNA expression profiles
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Updated: Jul 15, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Yukako Iitani1, Rika Miki2, Kenji Imai1
1Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466‑8550, Japan.
Background:
Increased maternal interleukin (IL)-17A and activated microglia are pivotal factors contributing to the pathological phenotypes of maternal immune activation (MIA), developing neurodevelopmental disorders in offspring. This study aimed to determine whether IL-17A affects the microglial microRNA (miRNA) profiles.
Methods:
The miRNA expression profiles of primary cultured microglia stimulated with recombinant IL-17A were examined comprehensively using miRNA sequencing and validated through qRT-PCR. The expressions of miRNAs target genes identified using bioinformatics, were investigated in microglia transfected with mimic miRNA. The target gene's expression was also examined in the fetal brains of the MIA mouse model induced by maternal lipopolysaccharide (LPS) administration.
Results:
Primary cultured microglia expressed the IL-17A receptor and increased proinflammatory cytokines and nitric oxide synthase 2 upon treatment with IL-17A. Among the three miRNAs with |log2FC | >1, only mmu-miR-206-3p expression was significantly up-regulated by IL-17A. Transfection with the mmu-miR-206-3p mimic resulted in a significant decrease in the expression of Hdac4 and Igf1, target genes of mmu-miR-206-3p. Hdac4 expression also significantly decreased in the LPS-induced MIA model.
Conclusions:
IL-17A affected microglial miRNA profiles with upregulated mmu-miR-206-3p. These findings suggest that targeting the IL-17A/mmu-miR-206-3p pathway may be a new strategy for predicting MIA-related neurodevelopmental deficits and providing preventive interventions.
Impact:
Despite the growing evidence of interleukin (IL)-17A and microglia in the pathology of maternal immune activation (MIA), the downstream of IL-17A in microglia is not fully known. IL-17A altered microRNA profiles and upregulated the mmu-miR-206-3p expression in microglia. The mmu-miR-206-3p reduced autism spectrum disorder (ASD) related gene expressions, Hdac4 and Igf1. The Hdac4 expression was also reduced in the brain of MIA offspring. The hsa-miR-206 sequence is consistent with that of mmu-miR-206-3p. This study may provide clues to pathological mechanisms leading to predictions and interventions for ASD children born to mothers with IL-17A-related disorders.
Insights
Maternal immune activation (MIA) involves interleukin-17A (IL-17A) and microglia. This study shows IL-17A upregulates microRNA-206 (miR-206) in microglia, potentially impacting neurodevelopmental disorders.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Maternal immune activation (MIA) is linked to neurodevelopmental disorders in offspring.
- Interleukin-17A (IL-17A) and activated microglia are key factors in MIA pathology.
- The precise downstream effects of IL-17A on microglia remain incompletely understood.
Purpose of the Study:
- To investigate the impact of IL-17A on microglial microRNA (miRNA) profiles.
- To identify specific miRNAs regulated by IL-17A in microglia.
- To explore the functional consequences of IL-17A-induced miRNA changes in the context of MIA.
Main Methods:
- Primary microglia were stimulated with IL-17A, and miRNA expression profiles were analyzed using sequencing and qRT-PCR.
- Bioinformatics identified target genes of differentially expressed miRNAs.
- Target gene expression was validated in microglia transfected with miRNA mimics and in a lipopolysaccharide (LPS)-induced MIA mouse model.
Main Results:
- IL-17A stimulation upregulated mmu-miR-206-3p expression in primary microglia.
- IL-17A-induced upregulation of mmu-miR-206-3p led to decreased expression of its target genes, Hdac4 and Igf1.
- Hdac4 expression was also significantly reduced in the fetal brains of the MIA mouse model.
Conclusions:
- IL-17A modulates microglial miRNA profiles, specifically upregulating mmu-miR-206-3p.
- The IL-17A/mmu-miR-206-3p pathway influences the expression of genes implicated in neurodevelopmental disorders.
- Targeting this pathway offers potential for predicting and intervening in MIA-related neurodevelopmental deficits, including autism spectrum disorder (ASD).
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