Splenic macrophages imprinted with an antioxidative program for tissue residency and homeostasis 9109
Bibliographic record
Abstract
Abstract Description M-CSF is crucial for the homeostasis of most tissue-resident macrophages, yet the underlying mechanisms may vary with specific macrophage subsets. In this regard, we found that while depriving M-CSF led to a universal reduction in tissue macrophages, only splenic macrophages were restored by simultaneous injection of antioxidant vitamin E Trolox. Mechanistically, M-CSF acts through its downstream effectors, especially mTOR, to coordinate the expression of an antioxidative program featured with ATF4/Slc7a11 and Gpx1/4 in the splenic macrophages. Genetic ablation or pharmacological blockade of mTOR led to diminished peritoneal, splenic and bone marrow macrophages. Strikingly, in vivo administering Trolox restored the splenic rather than peritoneal macrophages, supporting a tissue-specific role for the mTOR-regulated antioxidative program. Upon being challenged with chemical-induced hemolysis, the splenic macrophages also relied on mTOR/Gpx4 to constrain the oxidative stress following engulfing massive erythrocytes. Together, these results reveal a unique program required for splenic macrophage maintenance in homeostatic and pathologic settings. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)
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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) | 0.002 | 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".