USP22 maintains regulatory T cells by stabilizing Foxp3 protein level and impairs anti-tumor immune response
Bibliographic record
Abstract
Abstract Ubiquitin-specific peptidase 22, a member of the deubiquitinase family, has been recently defined as a "cancer stem cell" marker in tumor development and progression. However, the physiological function of USP22, particularly in the immune system, remains unknown. Here, we identify USP22 as a specific deubiquitinase of Foxp3, a lineage-specifying transcription factor of regulatory T (Treg) cells. A genetic deletion in USP22 results in a dramatic reduction in FoxP3 expression levels and impairs the suppressive functions of Tregs without affecting the activation of conventional T cells. Consequently, a targeted deletion of USP22 in mice, either specifically in T cells or in Tregs, results in chronic T cell activation and the development of spontaneous autoimmune syndromes. Importantly, the impairment in Treg suppressive function of USP22-null Tregs boosts anti-tumor immunity. Collectively, our findings reveal a previously unappreciated physiological function of USP22 in maintaining Treg stability and identify USP22 as a potential target for cancer immunotherapy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".