Adipose-Tissue-Derived Mesenchymal Stem Cells Mediate PD-L1 Overexpression in the White Adipose Tissue of Obese Individuals, Resulting in T Cell Dysfunction
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals, Diet, and Experimental Design
2.2. Tissue Collection and Blood and Plasma Analyses
2.3. Isolation and Expansion of Adipose-Tissue-Derived Mesenchymal Stem Cells
2.4. Isolation of Blood Mononuclear Cells (MNC)
2.5. Coculture Assays
2.6. mRNA Measurements
2.7. Flow Cytometry
2.8. Differentiation of Obese Subcutaneous ASC into AD
2.9. Immunohistochemistry
2.10. Statistical Analysis
3. Results
3.1. PD-L1 and/or PD-1 Are Overexpressed in the WAT of Obese Mice
3.2. Inflammation-Mediated by Adipose-Tissue-Derived Mesenchymal Stem Cells from Obese Individuals Contributes to PD-L1 Upregulation in Cocultures with Mononuclear Cells
3.3. Activation of T Cells Upregulates PD-1 Expression but Is Not Influenced by the Presence of Adipose-Derived Stem Cells (ASC)
3.4. PD-L1 Blockade Partially Restores Th1 Cell Secretion and Improves Ob-ASC Mediated Th17 Cell Activation, without Affecting Pro-Inflammatory Cytokine Secretion by Accessory Cells
3.5. Ob-ASC-Mediated Inflammation Results in Increasing PD-L1 Expression in Freshly Differentiated Adipocytes
4. Discussion
5. Limitations of the Study
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Eljaafari, A.; Pestel, J.; Le Magueresse-Battistoni, B.; Chanon, S.; Watson, J.; Robert, M.; Disse, E.; Vidal, H. Adipose-Tissue-Derived Mesenchymal Stem Cells Mediate PD-L1 Overexpression in the White Adipose Tissue of Obese Individuals, Resulting in T Cell Dysfunction. Cells 2021, 10, 2645. https://doi.org/10.3390/cells10102645
Eljaafari A, Pestel J, Le Magueresse-Battistoni B, Chanon S, Watson J, Robert M, Disse E, Vidal H. Adipose-Tissue-Derived Mesenchymal Stem Cells Mediate PD-L1 Overexpression in the White Adipose Tissue of Obese Individuals, Resulting in T Cell Dysfunction. Cells. 2021; 10(10):2645. https://doi.org/10.3390/cells10102645
Chicago/Turabian StyleEljaafari, Assia, Julien Pestel, Brigitte Le Magueresse-Battistoni, Stephanie Chanon, Julia Watson, Maud Robert, Emmanuel Disse, and Hubert Vidal. 2021. "Adipose-Tissue-Derived Mesenchymal Stem Cells Mediate PD-L1 Overexpression in the White Adipose Tissue of Obese Individuals, Resulting in T Cell Dysfunction" Cells 10, no. 10: 2645. https://doi.org/10.3390/cells10102645
APA StyleEljaafari, A., Pestel, J., Le Magueresse-Battistoni, B., Chanon, S., Watson, J., Robert, M., Disse, E., & Vidal, H. (2021). Adipose-Tissue-Derived Mesenchymal Stem Cells Mediate PD-L1 Overexpression in the White Adipose Tissue of Obese Individuals, Resulting in T Cell Dysfunction. Cells, 10(10), 2645. https://doi.org/10.3390/cells10102645