Peroxisome Proliferator-Activated Receptor Delta (PPARδ) activity is required for normal T cell development
Bibliographic record
Abstract
Abstract PPARδ is a nuclear receptor that functions as a transcriptional regulator of various processes including metabolic homeostasis, cell proliferation and differentiation; however, whether PPARδ regulates T cell development is not known. We observed that PPARδ-deficient (PPARδ−/−) mice have smaller spleens and thymi compared to wild-type (WT) mice. This reduction in thymus cellularity was apparent across all stages of thymocyte development. To further narrow in on the cellular basis of this effect, radiation bone marrow chimeras were generated where WT or PPARδ−/− mice were reconstituted with WT or PPARδ−/− bone marrow. These experiments clearly revealed that the defects in thymus and spleen mapped to the radio-resistant compartment. This was furthered confirmed by the finding that mice with T cell-restricted deficiency of PPARδ did not exhibit defective thymocyte homeostasis. Given that thymic epithelial cells (TECs) are the major radio-resistant cell population in the thymus, we next generated mice with a TEC-restricted deficiency of PPARδ (PPARδflox/floxFoxN1-Cre+). We observed that PPARδflox/floxFoxN1-Cre+ mice exhibit a trend for reduced thymus and spleen cellularity compared to PPARδflox/flox mice; however, this phenotype was not as striking as seen in PPARδ−/− mice. These results suggest that, in addition to acting within TECs, PPARδ may regulate the production of a circulating factor that in turn regulates thymocyte development. Large-scale serum profiling studies are underway to identify this factor. Altogether, this work highlights a role for PPARδ in T cell development.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".