Elevated IL-16 expression is associated with development of immune dysfunction in children with autism

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in communication skills and social behaviors. Several studies have suggested that neuroimmune dysfunction plays a significant role in the pathogenesis of ASD; however, its exact etiology is unknown. Interleukin-16 (IL-16), a chemoattractant, is associated with various inflammatory processes. However, its role in children with ASD is unclear. This study aimed to investigate whether IL-16 expression is associated with immune dysfunction in children with ASD. We examined IL-16 expression in CD4⁺, CD8⁺, CD14⁺, CCR3⁺, and CXCR7⁺ cells in typically developing (TD) controls and children with ASD using flow cytometry in peripheral blood mononuclear cells (PBMCs). We also investigated the expression of IL-1β⁺IL-16⁺, IL-6⁺IL-16⁺, and TNF-α⁺IL-16⁺ in TD controls and children with ASD. We further explored IL-16 mRNA and protein expression using RT-PCR and western blotting. CD4⁺IL-16⁺, CD8⁺IL-16⁺, CD14⁺IL-16⁺, CCR3⁺IL-16⁺, and CXCR7⁺IL-16⁺ cells increased significantly in children with ASD compared with TD controls. We also showed that expression of IL-1β⁺IL-16⁺, IL-6⁺IL-16⁺, and TNF-α⁺IL-16⁺ was elevated in children with ASD compared with TD controls. Moreover, IL-16 mRNA and protein expression was significantly induced in children with ASD compared with TD controls. These results suggest that IL-16 expression could play an essential role in immune alteration in children with ASD.

Keywords: Autism spectrum disorder; Cytokines; Interleukin-16; Peripheral blood mononuclear cells; Typically developing controls.