Invariant NKT cells are unusually refractory to glucocorticoid-induced apoptosis but exhibit impaired functional fitness and fail to trigger antitumor immunity following physiological stress
Bibliographic record
Abstract
Abstract The nervous system serves critical roles in the regulation of immune responses. Consequently, the neuroimmune functional interface can be disrupted by physiological stress, potentially impeding our ability to combat malignancies. Invariant natural killer T (iNKT) cells are innate-like T cells that, upon activation by lipids such as αGC, participate in antitumor immune surveillance. However, whether mediators of stress impact iNKT cell functions in this context remains unexplored. Here, we subjected mice to prolonged psychological stress due to physical restraint or chronic stress due to heterotypic stressors before administering αGC. We report that stress abrogates TH1-type cytokine production by iNKT cells in vivo, an effect that is reversible by glucocorticoid receptor (GR) blockade and that is diminished in mice selectively lacking GRs in their T cell compartment. Instead, iNKT cell responses are skewed towards an abnormal anti-inflammatory and TH17-type cytokine signature. Gene expression analysis revealed that iNKT cells in stressed mice express reduced levels of critical genes supporting their typical differentiation states. Accordingly, iNKT cells in stressed mice fail to protect against pulmonary metastases of B16-F10 melanoma and are also unable to initiate killing activity against MHC class I-deficient splenocytes in vivo or YAC-1 lymphoma cells in vitro. Finally, the suppressive effects of stress on iNKT cells are not due to their apoptotic death. Unlike conventional T cells, human and mouse iNKT cells are remarkably resistant to glucocorticoid-induced apoptosis. Collectively, our findings define a novel mechanism of stress-induced immunosuppression involving innate-like but not conventional T cells.
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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 | 0.001 |
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".