Interleukin-17A stimulation induces alterations in Microglial microRNA expression profiles

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).