Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism

• Published in: Molecular neurobiology Vol. 54; no. 6; pp. 4390 - 4400
• Main Authors: Ahmad, Sheikh Fayaz, Zoheir, Khairy M A, Ansari, Mushtaq Ahmad, Nadeem, Ahmed, Bakheet, Saleh A., AL-Ayadhi, Laila Yousef, Alzahrani, Mohammad Zeed, Al-Shabanah, Othman A., Al-Harbi, Mohammed M., Attia, Sabry M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2017; Springer Nature B.V
• Subjects: Autism; Autistic children; Autistic Disorder - genetics; Autistic Disorder - immunology; Biomedical and Life Sciences; Biomedicine; Brefeldin A; CD4 antigen; Cell Biology; Child; Child, Preschool; Children; Children & youth; Communications systems; Flow Cytometry; Foxp3 protein; GATA-3 protein; Helper cells; Humans; Immune system; Immunology; Ionomycin; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Neurobiology; Neurodevelopmental disorders; Neurology; Neurosciences; Peripheral blood mononuclear cells; Phorbol esters; Polymerase chain reaction; Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction; Signaling; Social behavior; Social interactions; Stat3 protein; T-Lymphocytes, Regulatory - immunology; Th1 Cells - immunology; Th17 Cells - immunology; Th2 Cells - immunology; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Peripheral blood mononuclear cells; Autism; CD4 T cells; Transcription factor; Interleukin
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-016-9977-0

Autism is a neurodevelopmental disorder characterized by stereotypic repetitive behaviors, impaired social interactions, and communication deficits. Numerous immune system abnormalities have been described in individuals with autism including abnormalities in the ratio of Th1/Th2/Th17 cells; however, the expression of the transcription factors responsible for the regulation and differentiation of Th1/Th2/Th17/Treg cells has not previously been evaluated. Peripheral blood mononuclear cells (PBMCs) from children with autism (AU) or typically developing (TD) control children were stimulated with phorbol-12-myristate 13-acetate (PMA) and ionomycin in the presence of brefeldin A. The expressions of Foxp3, RORγt, STAT-3, T-bet, and GATA-3 mRNAs and proteins were then assessed. Our study shows that children with AU displayed altered immune profiles and function, characterized by a systemic deficit of Foxp3 + T regulatory (Treg) cells and increased RORγt + , T-bet + , GATA-3 + , and production by CD4 + T cells as compared to TD. This was confirmed by real-time PCR (RT-PCR) and western blot analyses. Our results suggest that autism impacts transcription factor signaling, which results in an immunological imbalance. Therefore, the restoration of transcription factor signaling may have a great therapeutic potential in the treatment of autistic disorders.