Altered Transcriptional Regulation of Glycolysis in Circulating CD8<sup>+</sup> T Cells of Rheumatoid Arthritis Patients
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 al...
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MDPI AG
2022-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/7/1216 |
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| author | Shilpa Harshan Poulami Dey Srivatsan Raghunathan |
| author_facet | Shilpa Harshan Poulami Dey Srivatsan Raghunathan |
| author_sort | Shilpa Harshan |
| collection | DOAJ |
| description | 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<sup>+</sup> effector memory cells (Tem) and CD8<sup>+</sup>CD45RA<sup>+</sup> effector memory cells (Temra) showed large changes in the transcriptional regulation of glycolysis in untreated RA. <i>PFKFB3</i> and <i>GAPDH</i> were differentially regulated and had high centrality scores in CD8<sup>+</sup> Tem cells. <i>PFKFB3</i> downregulation may be due to <i>HIF1A</i> post transcriptional inhibition. Tocilizumab treatment partially reversed the RA-associated differential expression of several metabolic and regulatory genes. <i>MYC</i> was upregulated and had high centrality scores in RA CD8<sup>+</sup> Temra cells; however, its glycolysis targets were unaltered. The upregulation of the PI3K-AKT and mTOR pathways may explain <i>MYC</i> upregulation. |
| first_indexed | 2024-03-09T03:23:11Z |
| format | Article |
| id | doaj.art-0a38bdcaac04489bb491f25f876971f9 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T03:23:11Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-0a38bdcaac04489bb491f25f876971f92023-12-03T15:06:04ZengMDPI AGGenes2073-44252022-07-01137121610.3390/genes13071216Altered Transcriptional Regulation of Glycolysis in Circulating CD8<sup>+</sup> T Cells of Rheumatoid Arthritis PatientsShilpa Harshan0Poulami Dey1Srivatsan Raghunathan2Institute of Bioinformatics and Applied Biotechnology, Bangalore 560100, Karnataka, IndiaThe Edu Bio LLC, 2222 W. Grand River Ave, STE A, Okemos, MI 48864, USAInstitute of Bioinformatics and Applied Biotechnology, Bangalore 560100, Karnataka, IndiaPeripheral 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<sup>+</sup> effector memory cells (Tem) and CD8<sup>+</sup>CD45RA<sup>+</sup> effector memory cells (Temra) showed large changes in the transcriptional regulation of glycolysis in untreated RA. <i>PFKFB3</i> and <i>GAPDH</i> were differentially regulated and had high centrality scores in CD8<sup>+</sup> Tem cells. <i>PFKFB3</i> downregulation may be due to <i>HIF1A</i> post transcriptional inhibition. Tocilizumab treatment partially reversed the RA-associated differential expression of several metabolic and regulatory genes. <i>MYC</i> was upregulated and had high centrality scores in RA CD8<sup>+</sup> Temra cells; however, its glycolysis targets were unaltered. The upregulation of the PI3K-AKT and mTOR pathways may explain <i>MYC</i> upregulation.https://www.mdpi.com/2073-4425/13/7/1216rheumatoid arthritisT lymphocyteregulation of glycolysisRNA sequencing<i>PFKFB3</i>pentose phosphate pathway |
| spellingShingle | Shilpa Harshan Poulami Dey Srivatsan Raghunathan Altered Transcriptional Regulation of Glycolysis in Circulating CD8<sup>+</sup> T Cells of Rheumatoid Arthritis Patients Genes rheumatoid arthritis T lymphocyte regulation of glycolysis RNA sequencing <i>PFKFB3</i> pentose phosphate pathway |
| title | Altered Transcriptional Regulation of Glycolysis in Circulating CD8<sup>+</sup> T Cells of Rheumatoid Arthritis Patients |
| title_full | Altered Transcriptional Regulation of Glycolysis in Circulating CD8<sup>+</sup> T Cells of Rheumatoid Arthritis Patients |
| title_fullStr | Altered Transcriptional Regulation of Glycolysis in Circulating CD8<sup>+</sup> T Cells of Rheumatoid Arthritis Patients |
| title_full_unstemmed | Altered Transcriptional Regulation of Glycolysis in Circulating CD8<sup>+</sup> T Cells of Rheumatoid Arthritis Patients |
| title_short | Altered Transcriptional Regulation of Glycolysis in Circulating CD8<sup>+</sup> T Cells of Rheumatoid Arthritis Patients |
| title_sort | altered transcriptional regulation of glycolysis in circulating cd8 sup sup t cells of rheumatoid arthritis patients |
| topic | rheumatoid arthritis T lymphocyte regulation of glycolysis RNA sequencing <i>PFKFB3</i> pentose phosphate pathway |
| url | https://www.mdpi.com/2073-4425/13/7/1216 |
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