Serpine1 negatively regulates Th1 cell responses in experimental autoimmune encephalomyelitis
Bibliographic record
Abstract
Abstract Th1 cells are critical in experimental autoimmune encephalomyelitis (EAE). Serpine1 has been posited as an inhibitor of IFN γ from T cells though its role in autoimmunity remains unclear. Here, we show that Serpine1 knockout (KO) mice develop EAE of enhanced severity relative to wild-type (WT) controls. Serpine1 overexpression represses Th1 cell cytokine production and pathogenicity, while Serpine1-KO:2D2 Th1 cells transfer EAE of increased severity in comparison to WT 2D2 Th1 cells. Notably, polarized Serpine1-KO Th1 cells display delayed expression of the Th1-specific inhibitory receptor, Tim-3. Serpine1-KO:Tim-3-Tg Th1 cells, which transgenically over-express Tim-3, showed increased expression of IFN γ and reduced expression of the checkpoint molecules Lag-3 and PD-1 relative to WT Tim-3-Tg counterparts. Further, Serpine1 deficiency restored the EAE phenotype of Tim-3-Tg mice that normally develop mild disease. Together, we identify Serpine1 as a negative regulator of Th1 cells. Key points Serpine1 inhibits EAE in a T cell-dependent manner. Serpine1 is upregulated in Th1 cells and inhibits their pathogenicity. Serpine1 promotes expression and function of Th1-specific inhibitory receptor Tim-3.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".