Hypoxia-induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of mesenchymal stem cells
Bibliographic record
Abstract
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".