IL-33 Induces a Protective Response against Irritant-induced Airway Inflammation and Dysfunction
Bibliographic record
Abstract
Abstract IL-33 released by injurious stimuli to airway epithelium activates innate lymphoid cells (ILCs) that express IL-13. IL-33 and ILCs have an important role in type 2 (T2)-high asthma, but their influence on airway dysfunction induced by irritants is unclear. We examined the effects of Cl2 inhalation on IL-33 release, pulmonary ILCs, airway inflammation, and airway hyperresponsiveness (AHR). Cl2 exposure resulted in IL-33 release and increased ILC2s in the airways of BALB/c mice. Inhibition of the IL-33 receptor did not alter AHR, but depletion of ILCs augmented AHR. Recombinant IL-33 given for 3 successive days to wild-type and Rag1−/− (recombinant activating gene–deficient) mice, deficient in mature T and B cells, further increased ILC2s and inhibited Cl2-induced neutrophilia and AHR, whereas Rag−/− IL2rγ−/− mice, lacking ILCs, did not show these effects. IL-33 increased IL-13 expression by ILC2s, and IL-13 neutralization exacerbated AHR, whereas IL-13 administration reduced AHR in Cl2-exposed Rag1−/− mice. IL-33 biased alveolar macrophages toward the M2 phenotype, partly mediated by IL-13. Depletion with clodronate liposomes abrogated the IL-33 protective effect on AHR. The data suggest that the expansion of ILC2s by IL-33 activates a protective pathway involving IL-13 and macrophages against airway dysfunction and inflammation after inhalation of Cl2.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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".