Dysfunction and Metabolic Reprogramming of Gut Regulatory T Cells in HIV-Infected Immunological Non-Responders
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Subjects and Sample Processing
2.2. ScRNA-Seq Library Construction, Read Mapping and Quality Control
2.3. ScRNA-Seq Data Processing
2.4. Cell Annotation and Subpopulation Re-Analysis
2.5. Cell Distribution Discrepancy
2.6. Differentially Expressed Gene (DEG) Analysis
2.7. Functional Scoring
2.8. Trajectory Analysis
2.9. Faecal Microbiota Analysis
2.10. HIV DNA and CA HIV RNA Quantification
2.11. Detection of Plasma Short-Chain Fatty Acids
2.12. In Virto Stimulation
2.13. Detection of Cell Apoptosis and Cytokines
2.14. Detection of Cellular Energy Metabolism
2.15. Statistical Analysis
3. Results
3.1. Marginal Increase but Dysfunction of Gut Tregs in INRs
3.2. Transcriptional Profiling of Gut Treg Subsets in NCs, IRs, and INRs
3.3. Reprogrammed Energy Metabolism of Gut Tregs in INRs
3.4. Reduced in the Abundance of SCFA-Producing Bacteria and SCFA Concentration in INRs
3.5. SCFA Stimulation Restores Treg Dysfunction
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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NCs (n = 4) | IRs (n = 8) | INRs (n = 3) | p_Value | |
---|---|---|---|---|
Age (years) | 45 (39–46) | 40 (30–48) | 45 (40–49) | 0.497 |
Gender (Male/Female) | 4/0 | 8/0 | 3/0 | |
CD4+ T cell count (cells/µL) | 919 (844–980) | 861 (730–1006) | 135 (133–138) | 0.0206 * |
CD8+ T cell count (cells/µL) | 471 (424–527) | 1033 (877–1370) | 482 (479–597) | 0.0015 ** |
CD4/CD8 ratio | 2.01 (1.83–2.13) | 0.79 (0.73–0.92) | 0.27 (0.24–0.28) | <0.0001 **** |
Nadir CD4+ T cell count (cells/µL) | - | 352 (299–382) | 24 (10–53) | 0.0121 * |
ART duration (years) | - | 4 (3–6) | 4(3–5) | 0.63 |
ART regimen (%) | 1 | |||
2NRTIs+1NNRTIs | - | 5 (62.5%) | 2 (66.7%) | |
2NRTIs+1INSTIs | - | 3 (37.5%) | 1 (33.3%) |
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Yu, M.; Qu, M.; Wang, Z.; Zhen, C.; Yang, B.; Zhang, Y.; Huang, H.; Zhang, C.; Song, J.; Fan, X.; et al. Dysfunction and Metabolic Reprogramming of Gut Regulatory T Cells in HIV-Infected Immunological Non-Responders. Cells 2025, 14, 1164. https://doi.org/10.3390/cells14151164
Yu M, Qu M, Wang Z, Zhen C, Yang B, Zhang Y, Huang H, Zhang C, Song J, Fan X, et al. Dysfunction and Metabolic Reprogramming of Gut Regulatory T Cells in HIV-Infected Immunological Non-Responders. Cells. 2025; 14(15):1164. https://doi.org/10.3390/cells14151164
Chicago/Turabian StyleYu, Minrui, Mengmeng Qu, Zerui Wang, Cheng Zhen, Baopeng Yang, Yi Zhang, Huihuang Huang, Chao Zhang, Jinwen Song, Xing Fan, and et al. 2025. "Dysfunction and Metabolic Reprogramming of Gut Regulatory T Cells in HIV-Infected Immunological Non-Responders" Cells 14, no. 15: 1164. https://doi.org/10.3390/cells14151164
APA StyleYu, M., Qu, M., Wang, Z., Zhen, C., Yang, B., Zhang, Y., Huang, H., Zhang, C., Song, J., Fan, X., Xu, R., Jiao, Y.-M., & Wang, F.-S. (2025). Dysfunction and Metabolic Reprogramming of Gut Regulatory T Cells in HIV-Infected Immunological Non-Responders. Cells, 14(15), 1164. https://doi.org/10.3390/cells14151164