Assessment of Expression of Regulatory T Cell Differentiation Genes in Autism Spectrum Disorder

Mohammadarian Akbari; Reyhane Eghtedarian; Bashdar Mahmud Hussen; Solat Eslami; Mohammad Taheri; Seyedeh Morvarid Neishabouri; Soudeh Ghafouri-Fard

doi:10.3389/fnmol.2022.939224

Assessment of Expression of Regulatory T Cell Differentiation Genes in Autism Spectrum Disorder

Front Mol Neurosci. 2022 Jul 4:15:939224. doi: 10.3389/fnmol.2022.939224. eCollection 2022.

Authors

Mohammadarian Akbari¹, Reyhane Eghtedarian², Bashdar Mahmud Hussen^{3

4}, Solat Eslami^{5

6}, Mohammad Taheri⁷, Seyedeh Morvarid Neishabouri⁸, Soudeh Ghafouri-Fard⁹

Affiliations

¹ Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
² Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
⁴ Center of Research and Strategic Studies, Lebanese French University, Erbil, Iraq.
⁵ Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran.
⁶ Department of Medical Biotechnology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
⁷ Institute of Human Genetics, Jena University Hospital, Jena, Germany.
⁸ Department of Psychiatric, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁹ Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Dysfunction of regulatory T cells (Tregs) has been shown to affect the etiology of autism spectrum disorder (ASD). Differentiation of this group of T cells has been found to be regulated by a group of long non-coding RNAs (lncRNAs). In this study, we have examined the expression of five lncRNAs that regulate this process in the blood samples of ASD cases compared with controls. These lncRNAs were FOXP3 regulating long intergenic non-coding RNA (FLICR), MAF transcriptional regulator RNA (MAFTRR), NEST (IFNG-AS1), RNA component of mitochondrial RNA processing endoribonuclease (RMRP), and Th2 cytokine locus control region (TH2-LCR). Expression of RMRP was significantly lower in total ASD cases compared to controls [expression ratio (95% CI) = 0.11 (0.08-0.18), adjusted P-value < 0.0001]. This pattern was also detected in both men and women cases compared with corresponding controls [expression ratio (95% CI) = 0.15 (0.08-0.29) and 0.08 (0.03-0.2), respectively]. Likewise, expression of NEST was reduced in total cases and cases among men and women compared with corresponding controls [expression ratio (95% CI) = 0.2 (0.14-0.28); 0.22 (0.12-0.37); and 0.19 (0.09-0.43), respectively; adjusted P-value < 0.0001]. Lastly, FLICR was downregulated in total cases and cases among both boys and girls compared with matched controls [expression ratio (95% CI) = 0.1 (0.06-0.19); 0.19 (0.08-0.46); and 0.06 (0.01-0.21), respectively; adjusted P-value < 0.0001]. These three lncRNAs had appropriate diagnostic power for differentiation of ASD cases from controls. Cumulatively, our study supports dysregulation of Treg-related lncRNAs in patients with ASD and suggests these lncRNAs as proper peripheral markers for ASD.

Keywords: ASD; FLICR; MAFTRR; NEST; RMRP; TH2-LCR.