The pharmacopeia of helminth-derived metabolites driving tolerance in dendritic cells
Bibliographic record
Abstract
ABSTRACT Helminth infections can restore immune tolerance and suppress intestinal inflammation, yet the molecular mediators underlying these effects are poorly defined. Here, we show that nonpolar metabolites derived from the helminth Heligmosomoides polygyrus bakeri (HnpM) program dendritic cells (DCs) toward a tolerogenic DC (tolDC) phenotype. Adoptive transfer of HnpM-treated DCs significantly ameliorated DSS-induced intestinal inflammation in mice. Transcriptomic and metabolomic profiling revealed that HnpM induces early metabolic reprogramming followed by gene expression signatures characteristic of tolerogenic DCs that are shared by established tolDC-inducing agents. Together, these findings identify that helminth-derived metabolites are a novel source of small molecule therapeutics to restore immune tolerance in immune-mediated disorders. Summary Sentence Metabolites produced by Heligmosomoides polygyrus induce metabolic and transcriptional changes in DCs consistent with tolDCs, and adoptive transfer of these DCs attenuate DSS-induced intestinal inflammation.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 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".