IL-21, Inflammatory Cytokines and Hyperpolarized CD8+ T Cells Are Central Players in Lupus Immune Pathology
Abstract
:1. Introduction
2. Materials and Methods
2.1. Clinical Characteristics of SLE Patients and Demography
2.2. Whole-Blood and PBMC Phenotyping from SLE Patients and Healthy Controls
2.3. Plasma Cytokine Detection Assay
2.4. Differentiation of CD8+ T Cells to Tc1 or Tc21 Cells from Healthy Controls
2.5. Cellular and Mitochondrial ROS from Healthy Controls and SLE CD8+ T Cells
2.6. Oxidant and Antioxidant Treatment of CD8+ T Cells
2.7. Intracellular Staining for Cytokines and Transcription Factors
2.8. Phospho-STAT Staining for Flow Cytometry
2.9. Phospho-mTOR Staining for Flow Cytometry
2.10. Statistics
3. Results
3.1. SLE CD8+ T Cells Display Higher CXCR5 and ICOS and Altered Compartments
3.2. SLE Patients Display Higher Pro-Inflammatory Cytokine Profile
3.3. SLE CD8+ T Cells Display Higher ROS and Mitochondrial Hyperpolarization
3.4. Redox Controls Pro- and Anti-Inflammatory Markers in SLE CD8+ T Cells
3.5. Modulating ROS Reduces p-STAT4 and p-mTOR from SLE CD8+ T Cells
3.6. Effector Tc1 Cells Exhibit ROS Sensitivity
3.7. ROS Induces Expression of p-STAT3 from Tc1 Cells
3.8. IL-21 Polarizes Tc1 Cell towards More Inflammatory Phenotype
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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HC (n = 26) | SLE (n = 41) | |
---|---|---|
Age, years, median (IQR) | 28 (25–34) | 25 (23–32) |
Sex, female/male, n (%) | 21 (80.76%)/5 (19.23%) | 40 (97.5%)/1 (2.4%) |
SLEDAI, median (IQR) | N.A | 5 (3–6) |
Anti-dsDNA, ELISA, U/mL, median (IQR) | N.D | 35.28 (10.89–74.72) |
C3, g/L, median (IQR) | N.D | 0.96 (0.64–1.25) |
C4, g/L, median (IQR) | N.D | 0.2 (0.19–0.25) |
CRP, mg/L, median (IQR) | N.D | 7.57 (5.78–16.24) |
History of nephritis | N.A | 5 |
Current drug use | ||
Prednisolone, n/n, % | N.A | 41/41, 100% |
Hydroxychloroquine, n/n, % | N.A | 41/41, 100% |
Azathioprine, n/n, % | N.A | 14/41, 34.16% |
Mycophenolate Mofetil, n/n, % | N.A | 24/41, 58.53% |
Methotrexate, n/n, % | N.A | 12/41, 29.26% |
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Sengupta, S.; Bhattacharya, G.; Mohanty, S.; Shaw, S.K.; Jogdand, G.M.; Jha, R.; Barik, P.K.; Parida, J.R.; Devadas, S. IL-21, Inflammatory Cytokines and Hyperpolarized CD8+ T Cells Are Central Players in Lupus Immune Pathology. Antioxidants 2023, 12, 181. https://doi.org/10.3390/antiox12010181
Sengupta S, Bhattacharya G, Mohanty S, Shaw SK, Jogdand GM, Jha R, Barik PK, Parida JR, Devadas S. IL-21, Inflammatory Cytokines and Hyperpolarized CD8+ T Cells Are Central Players in Lupus Immune Pathology. Antioxidants. 2023; 12(1):181. https://doi.org/10.3390/antiox12010181
Chicago/Turabian StyleSengupta, Soumya, Gargee Bhattacharya, Subhasmita Mohanty, Shubham K. Shaw, Gajendra M. Jogdand, Rohila Jha, Prakash K. Barik, Jyoti R. Parida, and Satish Devadas. 2023. "IL-21, Inflammatory Cytokines and Hyperpolarized CD8+ T Cells Are Central Players in Lupus Immune Pathology" Antioxidants 12, no. 1: 181. https://doi.org/10.3390/antiox12010181
APA StyleSengupta, S., Bhattacharya, G., Mohanty, S., Shaw, S. K., Jogdand, G. M., Jha, R., Barik, P. K., Parida, J. R., & Devadas, S. (2023). IL-21, Inflammatory Cytokines and Hyperpolarized CD8+ T Cells Are Central Players in Lupus Immune Pathology. Antioxidants, 12(1), 181. https://doi.org/10.3390/antiox12010181