Dysregulated gene expression associated with inflammatory and translation pathways in activated monocytes from children with autism spectrum disorder

Heather K. Hughes, Megan E. Rowland, Charity E. Onore, Sally Rogers, Annie Vogel Ciernia, Paul Ashwood

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Autism spectrum disorder (ASD) is a complex developmental disorder characterized by deficits in social interactions, communication, and stereotypical behaviors. Immune dysfunction is a common co-morbidity seen in ASD, with innate immune activation seen both in the brain and periphery. We previously identified significant differences in peripheral monocyte cytokine responses after stimulation with lipoteichoic acid (LTA) and lipopolysaccharide (LPS), which activate toll-like receptors (TLR)−2 and 4 respectively. However, an unbiased examination of monocyte gene expression in response to these stimulants had not yet been performed. To identify how TLR activation impacts gene expression in ASD monocytes, we isolated peripheral blood monocytes from 26 children diagnosed with autistic disorder (AD) or pervasive developmental disorder—not otherwise specified (PDDNOS) and 22 typically developing (TD) children and cultured them with LTA or LPS for 24 h, then performed RNA sequencing. Activation of both TLR2 and TLR4 induced expression of immune genes, with a subset that were differentially regulated in AD compared to TD samples. In response to LPS, monocytes from AD children showed a unique increase in KEGG pathways and GO terms that include key immune regulator genes. In contrast, monocytes from TD children showed a consistent decrease in expression of genes associated with translation in response to TLR stimulation. This decrease was not observed in AD or PDDNOS monocytes, suggesting a failure to properly downregulate a prolonged immune response in monocytes from children with ASD. As monocytes are involved in early orchestration of the immune response, our findings will help elucidate the mechanisms regulating immune dysfunction in ASD.

Original languageEnglish (US)
Article number39
JournalTranslational psychiatry
Volume12
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Fingerprint

Dive into the research topics of 'Dysregulated gene expression associated with inflammatory and translation pathways in activated monocytes from children with autism spectrum disorder'. Together they form a unique fingerprint.

Cite this