Hypoxia-induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of mesenchymal stem cells
| Autor: | Sanjiv Dhingra, Keshav Narayan Alagarsamy, Alireza Rafieerad, Weiang Yan, Vincenzo Desiderio, Ejlal Abu-El-Rub, Niketa Sareen, Abhay Srivastava |
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| Přispěvatelé: | Abu-El-Rub, E., Sareen, N., Yan, W., Alagarsamy, K. N., Rafieerad, A., Srivastava, A., Desiderio, V., Dhingra, S. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cell death
Cancer Research Proteasome Endopeptidase Complex Cell Immunology Down-Regulation HLA-DR alpha-Chains Human leukocyte antigen Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Immune system Downregulation and upregulation Antigen Medicine Humans lcsh:QH573-671 030304 developmental biology 0303 health sciences business.industry lcsh:Cytology Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology Cell Hypoxia 3. Good health Up-Regulation Transplantation Protein Subunits medicine.anatomical_structure Phenotype Proteasome 030220 oncology & carcinogenesis Proteolysis Cancer research business |
| Zdroj: | Cell Death and Disease, Vol 11, Iss 6, Pp 1-12 (2020) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Allogeneic mesenchymal stem cells (MSCs) are immunoprivileged and are being investigated in phase I and phase II clinical trials to treat different degenerative and autoimmune diseases. In spite of encouraging outcome of initial trials, the long-term poor survival of transplanted cells in the host tissue has declined the overall enthusiasm. Recent analyses of allogeneic MSCs based studies confirm that after transplantation in the hypoxic or ischemic microenvironment of diseased tissues, MSCs become immunogenic and are rejected by recipient immune system. The immunoprivilege of MSCs is preserved by absence or negligible expression of cell surface antigen, human leukocyte antigen (HLA)-DRα. We found that in normoxic MSCs, 26S proteasome degrades HLA-DRα and maintains immunoprivilege of MSCs. The exposure to hypoxia leads to inactivation of 26S proteasome and formation of immunoproteasome in MSCs, which is associated with upregulation and activation of HLA-DRα, and as a result, MSCs become immunogenic. Furthermore, inhibition of immunoproteasome formation in hypoxic MSCs preserves the immunoprivilege. Therefore, hypoxia-induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of allogeneic MSCs. The outcome of the current study may provide molecular targets to plan interventions to preserve immunoprivilege of allogeneic MSCs in the hypoxic or ischemic environment. |
| Databáze: | OpenAIRE |
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