Targeting of Phospholipase D1 Ameliorates Collagen-Induced Arthritis via Modulation of Treg and Th17 Cell Imbalance and Suppression of Osteoclastogenesis
Abstract
:1. Introduction
2. Results
2.1. Deficiency of PLD1 Results in Reduced CIA Severity
2.2. PLD1 Ablation Suppresses Collagen Type II-Specific Humoral Response and Production of Proinflammatory Cytokines in CIA Mice
2.3. PLD1 Ablation Regulates the Population of Th17 and Treg Cells
2.4. Pharmacological Inhibition of PLD1 Ameliorates Arthritis and Bone Erosion in CIA Mice
2.5. PLD1 Inhibition Suppresses the Production of Anti-CII IgG2a and Proinflammatory Cytokines in CIA Mice
2.6. Targeting PLD1 Increases the Population of Foxp3+ Treg Cells, Reduces the Population of Th17 Cells and Proliferation of Effector T Cells
2.7. Targeting PLD1 Reduces Osteoclastogenesis and Bone Resorption
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Mice and CIA
4.3. Micro-CT
4.4. Measurement of Type II Collagen-Specific Autoantibodies
4.5. Cytokine Analysis
4.6. q-PCR
4.7. Flow Cytometric Analysis
4.8. In Vitro Differentiation of Th Cells
4.9. In Vitro Treg Cell Suppression Assay
4.10. Immunofluorescence Staining
4.11. TRAP Staining
4.12. In Vitro Osteoclastogenesis Assay
4.13. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
PLD1 | Phospholipase D1 |
CIA | Collagen-induced arthritis |
RA | Rheumatoid arthritis |
RASF | Rheumatoid arthritis and synovial fibroblasts |
Treg | Regulatory T cells |
RANKL | Receptor activator of nuclear factor-κB ligand |
TRAP | Tartrate-resistant acid phosphatase |
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Yoo, H.J.; Hwang, W.C.; Min, D.S. Targeting of Phospholipase D1 Ameliorates Collagen-Induced Arthritis via Modulation of Treg and Th17 Cell Imbalance and Suppression of Osteoclastogenesis. Int. J. Mol. Sci. 2020, 21, 3230. https://doi.org/10.3390/ijms21093230
Yoo HJ, Hwang WC, Min DS. Targeting of Phospholipase D1 Ameliorates Collagen-Induced Arthritis via Modulation of Treg and Th17 Cell Imbalance and Suppression of Osteoclastogenesis. International Journal of Molecular Sciences. 2020; 21(9):3230. https://doi.org/10.3390/ijms21093230
Chicago/Turabian StyleYoo, Hyun Jung, Won Chan Hwang, and Do Sik Min. 2020. "Targeting of Phospholipase D1 Ameliorates Collagen-Induced Arthritis via Modulation of Treg and Th17 Cell Imbalance and Suppression of Osteoclastogenesis" International Journal of Molecular Sciences 21, no. 9: 3230. https://doi.org/10.3390/ijms21093230