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Article

Upregulation of Inflammatory Mediators in Peripheral Blood CD40+ Cells in Children with Autism Spectrum Disorder

by
Abdullah A. Aldossari
1,
Mushtaq A. Ansari
1,
Ahmed Nadeem
1,
Sabry M. Attia
1,
Saleh A. Bakheet
1,
Laila Y. Al-Ayadhi
2,
Mohammed M. Alanazi
1,
Mudassar Shahid
3,
Mohammad Y. Alwetaid
4,
Marwa H. Hussein
1 and
Sheikh F. Ahmad
1,*
1
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
2
Department of Physiology, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
3
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
4
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(8), 7475; https://doi.org/10.3390/ijms24087475
Submission received: 19 March 2023 / Revised: 11 April 2023 / Accepted: 13 April 2023 / Published: 19 April 2023
(This article belongs to the Special Issue Intercellular and Intracellular Communication in Human Health and Disease 2.0)
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Abstract

Autism spectrum disorder (ASD) is a common and severe neurodevelopmental disorder in early childhood, defined as social and communication deficits and repetitive and stereotypic behaviours. The aetiology is unknown in most cases. However, several studies have identified immune dysregulation as potentially promoting ASD. Among the numerous immunological findings in ASD, reports of increased pro-inflammatory markers remain the most consistently observed. C-C chemokine receptor type 1 (CCR1) activation is pro-inflammatory in several neurological disorders. Previous evidence has implied that the expression of chemokine receptors, inflammatory mediators, and transcription factors play a pivotal role in several neuroinflammatory disorders. There have also been reports on the association between increased levels of proinflammatory cytokines and ASD. In this study, we aimed to investigate the possible involvement of CCR1, inflammatory mediators, and transcription factor expression in CD40+ cells in ASD compared to typically developing controls (TDC). Flow cytometry analysis was used to determine the levels of CCR1-, IFN-γ-, T-box transcription factor (T-bet-), IL-17A-, retinoid-related orphan receptor gamma t (RORγt-), IL-22- and TNF-α-expressing CD40 cells in PBMCs in children with ASD and the TDC group. We further examined the mRNA and protein expression levels of CCR1 using real-time PCR and western blot analysis. Our results revealed that children with ASD had significantly increased numbers of CD40+CCR1+, CD40+IFN-γ+, CD40+T-bet+, CD40+IL-17A+, CD40+RORγt+, CD4+IL-22+, and CD40+TNF-α+ cells compared with the TDC group. Furthermore, children with ASD had higher CCR1 mRNA and protein expression levels than those in the TDC group. These results indicate that CCR1, inflammatory mediators, and transcription factors expressed in CD40 cells play vital roles in disease progression.
Keywords: autism spectrum disorder; cytokines; CD40; CCR1; PBMCs; transcription factors autism spectrum disorder; cytokines; CD40; CCR1; PBMCs; transcription factors

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MDPI and ACS Style

Aldossari, A.A.; Ansari, M.A.; Nadeem, A.; Attia, S.M.; Bakheet, S.A.; Al-Ayadhi, L.Y.; Alanazi, M.M.; Shahid, M.; Alwetaid, M.Y.; Hussein, M.H.; et al. Upregulation of Inflammatory Mediators in Peripheral Blood CD40+ Cells in Children with Autism Spectrum Disorder. Int. J. Mol. Sci. 2023, 24, 7475. https://doi.org/10.3390/ijms24087475

AMA Style

Aldossari AA, Ansari MA, Nadeem A, Attia SM, Bakheet SA, Al-Ayadhi LY, Alanazi MM, Shahid M, Alwetaid MY, Hussein MH, et al. Upregulation of Inflammatory Mediators in Peripheral Blood CD40+ Cells in Children with Autism Spectrum Disorder. International Journal of Molecular Sciences. 2023; 24(8):7475. https://doi.org/10.3390/ijms24087475

Chicago/Turabian Style

Aldossari, Abdullah A., Mushtaq A. Ansari, Ahmed Nadeem, Sabry M. Attia, Saleh A. Bakheet, Laila Y. Al-Ayadhi, Mohammed M. Alanazi, Mudassar Shahid, Mohammad Y. Alwetaid, Marwa H. Hussein, and et al. 2023. "Upregulation of Inflammatory Mediators in Peripheral Blood CD40+ Cells in Children with Autism Spectrum Disorder" International Journal of Molecular Sciences 24, no. 8: 7475. https://doi.org/10.3390/ijms24087475

APA Style

Aldossari, A. A., Ansari, M. A., Nadeem, A., Attia, S. M., Bakheet, S. A., Al-Ayadhi, L. Y., Alanazi, M. M., Shahid, M., Alwetaid, M. Y., Hussein, M. H., & Ahmad, S. F. (2023). Upregulation of Inflammatory Mediators in Peripheral Blood CD40+ Cells in Children with Autism Spectrum Disorder. International Journal of Molecular Sciences, 24(8), 7475. https://doi.org/10.3390/ijms24087475

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