Disequilibrium in the Thioredoxin Reductase-1/Thioredoxin-1 Redox Couple Is Associated with Increased T-Cell Apoptosis in Children with Autism

• Published in: Metabolites Vol. 13; no. 2; p. 286
• Main Authors: Alshehri, Samiyah, Nadeem, Ahmed, Ahmad, Sheikh F., Alqarni, Sana S., Al-Harbi, Naif O., Al-Ayadhi, Laila Y., Attia, Sabry M., Alqarni, Saleh A., Bakheet, Saleh A.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.02.2023; MDPI
• Subjects: Annexin V; Antioxidants; Apoptosis; ASD; Autism; Autistic children; Cell culture; Children; Complications and side effects; Development and progression; Dysbacteriosis; Environmental factors; Enzymatic activity; Flow cytometry; Health aspects; immune system; Immunologic diseases; inflammation; Inflammatory diseases; Language; Lipopolysaccharides; Lymphocytes; Lymphocytes T; Mental disorders; Oxidation-reduction reaction; Pediatric research; Pervasive developmental disorders; Phlebotomy; Physiological aspects; Proteins; Risk factors; Social behavior; Software; Stereotyped behavior; T cells; Thioredoxin; Trx1; TrxR1; Variance analysis; Saudi Arabia; United States > US; Riyadh Saudi Arabia; Trx1; ASD; inflammation; immune system; apoptosis; T cells; TrxR1
• ISSN: 2218-1989; 2218-1989
• DOI: 10.3390/metabo13020286

Autism spectrum disorder (ASD) is a neuropsychiatric childhood disorder that affects social skill and language development, and is characterized by persistent stereotypic behaviors, restricted social interests, and impaired language/social skills. ASD subjects have dysregulated immune responses due to impairment in inflammatory and antioxidant signaling in immune cells, such as T cells. Thioredoxin reductase-1 (TrxR1) and thioredoxin-1 (Trx1) play a crucial role in the maintenance of redox equilibrium in several immune cells, including T cells. T-cell apoptosis plays a crucial role in the pathogenesis of several inflammatory diseases. However, it remains to be explored how the TrxR1/Trx1 redox couple affects T-cells apoptosis in ASD and typically developing control (TDC) groups. Therefore, this single-center cross-sectional study explored the expression/activity of TrxR1/Trx1, and Bcl2, 7-AAD/annexin V immunostaining in T cells of ASD (n = 25) and TDC (n = 22) groups. Further, effects of the LPS were determined on apoptosis in TDC and ASD T cells. Our data show that T cells have increased TrxR1 expression, while having decreased Trx1 expression in the ASD group. Further, TrxR enzymatic activity was also elevated in T cells of the ASD group. Furthermore, T cells of the ASD group had a decreased Bcl2 expression and an increased % of annexin V immunostaining. Treatment of T cells with LPS caused greater apoptosis in the ASD group than the TDC group, with same treatment. These data reveal that the redox couple TrxR1/Trx1 is dysregulated in T cells of ASD subjects, which is associated with decreased Bcl2 expression and increased apoptosis. This may lead to decreased survival of T cells in ASD subjects during chronic inflammation. Future studies should investigate environmental factors, such as gut dysbiosis and pollutants, that may cause abnormal immune responses in the T cells of ASD subjects due to chronic inflammation.