Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism
| Autor: | Saleh A. Bakheet, Mushtaq A. Ansari, Mohammed M. Al-Harbi, Laila Y. Al-Ayadhi, Othman A. Al-Shabanah, Sheikh F. Ahmad, Ahmed Nadeem, Sabry M. Attia, Khairy M.A. Zoheir, Mohammad Z. Alzahrani |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Neuroscience (miscellaneous) chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Peripheral blood mononuclear cell 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Th2 Cells 0302 clinical medicine Immune system Neurodevelopmental disorder RAR-related orphan receptor gamma medicine Humans RNA Messenger Autistic Disorder Child Transcription factor FOXP3 hemic and immune systems Th1 Cells Flow Cytometry medicine.disease 030104 developmental biology Neurology chemistry Child Preschool Ionomycin Immunology Th17 Cells Autism 030217 neurology & neurosurgery Signal Transduction Transcription Factors |
| Zdroj: | Molecular Neurobiology. 54:4390-4400 |
| ISSN: | 1559-1182 0893-7648 |
| DOI: | 10.1007/s12035-016-9977-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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