STAT6-dependent regulation of airway inflammatory responses via OX40L expression on dendritic cells (IRC4P.610)
Bibliographic record
Abstract
Abstract Epithelial and other structural cells drive Th2 responses in vivo indirectly upon TLR4 or NOD receptor stimulation and production TSLP and other innate cytokines, which upregulate OX40L on dendritic cells (DCs). These DCs are potent inducers of Th2 cell differentiation. We have investigated the ability of a cell penetrating peptide targeting STAT6, STAT6-IP, to modulate OX40L expression and inhibit Th2 responses. Bone marrow derived CD11c+ DCs (BMDCs) were incubated with OVA (containing LPS) ± STAT6-IP (or control peptides) and MFI of OX40L surface expression was quantified by FACS. OVA-induced increases in OX40L MFI were reduced by STAT6-IP. Our data suggest that STAT6-IP treated, OVA-loaded BMDCs also have reduced Th2 cytokine production from target CD4+ T cells. In vivo, lung OX40L mRNA levels increased in OVA+MDP (a NOD2 agonist) treated mice were inhibited by STAT6-IP treatment. Airway inflammatory responses were assessed in OVA+MDP (± STAT6-IP) treated mice, upon OVA challenge 28 days later. Lung resistance, bronchoalveolar lavage levels of eosinophils and neutrophils, Th2 cytokine production & TARC mRNA levels were all reduced by STAT6-IP treatment at the time of OVA+MDP sensitization. Our data are consistent with a model in which STAT6-IP inhibits antigen-induced OX40L expression on DCs, reducing Th2 cytokine production from target T cells and the subsequent Th2-biased airway inflammatory responses that contribute to pathogenesis in allergic airways disease.
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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) | 0.003 | 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".