Peanut allergic humans display increased Ag-dependent IL-33/IL-33R responses that regulate recall responses (P6241)
Bibliographic record
Abstract
Abstract Peanut allergy is severe and persistent. IL-33 plays key roles in modulating murine Th2-like responses, shaping serum Ig production, and anaphylactic shock. The potential involvement of IL-33 and receptor components ST2 or IL-1RAcP in food allergy is unexplored as is the impact blocking endogenous IL-33 function. We hypothesized that (i) peanut allergic humans exhibit elevated systemic production and responsiveness to IL-33 vs non-allergic controls and (ii) that neutralizing endogenous IL-33 inhibits undesirable Ag-specific recall responses characteristic of food allergy. Acute peanut-driven restimulation revealed elevated IL-33, ST2 and IL-1RAcP production by PBMC of both peanut allergic and clinically tolerant groups (p<0.001). The intensity of peanut-dependent IL-33 mRNA production is linked to clinical phenotype(p<0.0006). Exogenous IL-33 increased Ag-driven CD4 T cell dependent IL-5, IL-9, IL-13 in both groups, with allergic volunteers most responsive (p<0.005). Soluble IL-33 receptors sST2-Fc and sIL-1RAcP-Fc inhibit elevated IL-5,9,13 recall responses in peanut allergic humans by median 80% (p<0.005). Thus, the data reveal a hitherto unrecognized and prominent role for excessive IL-33/IL-33R production and responsiveness in food allergic humans. Unexpectedly potent inhibition of peanut Ag-driven Type 2 recall responses in peanut-allergic individuals by sIL-33R components suggests potential therapeutic utility in food allergy and other human allergic disorders.
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.002 |
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; both teacher heads agree on what is shown here.
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".