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Article

Altered Transcriptional Regulation of Glycolysis in Circulating CD8+ T Cells of Rheumatoid Arthritis Patients

1
Institute of Bioinformatics and Applied Biotechnology, Bangalore 560100, Karnataka, India
2
Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
3
The Edu Bio LLC, 2222 W. Grand River Ave, STE A, Okemos, MI 48864, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Qiongyi Zhao and Pei Hao
Genes 2022, 13(7), 1216; https://doi.org/10.3390/genes13071216
Received: 7 April 2022 / Revised: 1 July 2022 / Accepted: 4 July 2022 / Published: 7 July 2022
(This article belongs to the Special Issue Bioinformatic Analysis of NGS Data)
Peripheral T lymphocytes of rheumatoid arthritis (RA) patients show pathological changes in their metabolic pathways, especially glycolysis. These changes may drive the increased proliferation and tissue invasiveness of RA T cells. In order to study the transcriptional regulation underlying these alterations, we analysed publicly available RNA sequencing data from circulating T lymphocyte subsets of healthy individuals, untreated RA patients, and patients undergoing treatment for RA. Differential co-expression networks were created using sample-wise edge weights from an analysis called “linear interpolation to obtain network estimates for single sample” (lionessR), and annotated using the Gene Transcription Regulation Database (GTRD). Genes with high centrality scores were identified. CD8+ effector memory cells (Tem) and CD8+CD45RA+ effector memory cells (Temra) showed large changes in the transcriptional regulation of glycolysis in untreated RA. PFKFB3 and GAPDH were differentially regulated and had high centrality scores in CD8+ Tem cells. PFKFB3 downregulation may be due to HIF1A post transcriptional inhibition. Tocilizumab treatment partially reversed the RA-associated differential expression of several metabolic and regulatory genes. MYC was upregulated and had high centrality scores in RA CD8+ Temra cells; however, its glycolysis targets were unaltered. The upregulation of the PI3K-AKT and mTOR pathways may explain MYC upregulation. View Full-Text
Keywords: rheumatoid arthritis; T lymphocyte; regulation of glycolysis; RNA sequencing; PFKFB3; pentose phosphate pathway; GAPDH; MYC; HIF1A; mTOR rheumatoid arthritis; T lymphocyte; regulation of glycolysis; RNA sequencing; PFKFB3; pentose phosphate pathway; GAPDH; MYC; HIF1A; mTOR
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MDPI and ACS Style

Harshan, S.; Dey, P.; Raghunathan, S. Altered Transcriptional Regulation of Glycolysis in Circulating CD8+ T Cells of Rheumatoid Arthritis Patients. Genes 2022, 13, 1216. https://doi.org/10.3390/genes13071216

AMA Style

Harshan S, Dey P, Raghunathan S. Altered Transcriptional Regulation of Glycolysis in Circulating CD8+ T Cells of Rheumatoid Arthritis Patients. Genes. 2022; 13(7):1216. https://doi.org/10.3390/genes13071216

Chicago/Turabian Style

Harshan, Shilpa, Poulami Dey, and Srivatsan Raghunathan. 2022. "Altered Transcriptional Regulation of Glycolysis in Circulating CD8+ T Cells of Rheumatoid Arthritis Patients" Genes 13, no. 7: 1216. https://doi.org/10.3390/genes13071216

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