Downregulation in Helios transcription factor signaling is associated with immune dysfunction in blood leukocytes of autistic children

Abstract

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder in which immunological imbalance has been suggested to be a major etiological component. Helios, a transcription factor, has been studied extensively in the context of human T cell regulation in health and disease, yet the role of Helios signaling has not been examined in children with ASD. In the present study, we investigated the production of Helios in CD4⁺, CD8⁺, and TIM-3⁺, CXCR3⁺ cells in typically developing (TD) controls and children with ASD and in peripheral blood mononuclear cells (PBMCs). We assayed the production of IFN-γ⁺Helios⁺, IL-21⁺Helios⁺, T-bet⁺Helios⁺, and Foxp3⁺Helios⁺ cells, and determined Helios mRNA and protein expression levels in PBMCs, in TD controls and children with ASD. Our results revealed that children with ASD had lower numbers of CD4⁺Helios⁺ CD8⁺Helios⁺, TIM-3⁺Helios⁺, and CXCR3⁺Helios⁺ cells as compared to TD controls. Our results also showed that children with ASD had decreased IFN-γ⁺Helios⁺, IL-21⁺Helios⁺, T-bet⁺Helios⁺, and Helios⁺Foxp3⁺ production compared to that in TD controls. Moreover, our results indicated that children with ASD had lower Helios mRNA and protein expression levels compared to those in TD controls. These results suggest that the Helios transcription factor may be critical to immune alterations in children with ASD. Therefore, our results suggest that targeting Helios signaling might offer a strategy for developing ASD therapies.

Keywords: Autism spectrum disorder; Cytokine; Helios; Peripheral blood mononuclear cell; Typically developing control.