Peripheral IL-6/IL-17/NF-κB1 and IL-10 Signaling in Children with Autism Spectrum Disorder: Integrative...

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Autism spectrum disorder (ASD) is linked to immune and inflammatory dysregulation.
• The molecular links between peripheral immune signals and neuroinflammation in ASD are not well understood.

Purpose of the Study:

• To investigate inflammation-related molecular pathways in ASD using integrated transcriptomic network analysis.
• To validate key cytokine genes (IL6, IL10, IL17, NF-κB1) using quantitative real-time polymerase chain reaction (qRT-PCR).

Main Methods:

• Integrative computational-experimental approach using four gene expression omnibus (GEO) transcriptomic datasets.
• Construction of protein-protein interaction (PPI) networks to identify inflammation-related modules.
• Validation of selected inflammatory genes (IL6, IL10, IL17, NF-κB1) via qRT-PCR in peripheral blood samples from ASD patients and healthy controls.

Main Results:

• Identification of core differentially expressed genes (DEGs) and a connected PPI network with hub genes (PUM1, TRRAP, ILF3, INO80, PTBP1).
• Functional enrichment analysis indicated cytokine-mediated signaling, leukocyte activation, and neuroinflammation.
• qRT-PCR confirmed significant dysregulation of IL6, IL17, NF-κB1, and IL10 in ASD peripheral blood samples.

Conclusions:

• A central pro-inflammatory axis (IL-6/IL-17/NF-κB1) and reduced IL-10 regulation were identified in ASD.
• Peripheral immune activation and transcriptional regulators are implicated in ASD neuroinflammation.
• Identified hub genes and pathways may serve as biomarkers and therapeutic targets for an inflammation-associated ASD subtype.