Chronic allergic lung inflammation drives ILC2 dysfunction and transdifferentiation to IL-17A-producing ILC3s, promoting emphysema development 2272
Bibliographic record
Abstract
Abstract Description Group 2 innate lymphoid cells (ILC2s) are activated by epithelial alarmins like IL-33, IL-25, and TSLP and produce type 2 cytokines IL-5 and IL-13, leading to eosinophilia and mucus hyperproduction in allergic inflammation. However, their role in chronic allergic inflammation remains unclear. We established a chronic allergic lung inflammation mouse model using repeated intranasal Alternaria alternata and papain injections. In the first three weeks of treatment, ILC2s expanded and produced type 2 cytokines, causing lung eosinophilia and mucus production. However, after five weeks, ILC2 numbers decreased, produced less cytokines and proliferated minimally. FACS analysis showed a small population of TIGIT+ ILC2s that were unresponsive to IL-33 and IL-7, indicating dysfunction. Unexpectedly, ILC3s also expanded, and some ILCs expressed both GATA3 and Rorγt and produced IL-5 and IL-17, suggesting ILC2-ILC3 transdifferentiation. In IL-33-KO mice, ILC2 expansion and ILC3 increase were prevented, supporting this transdifferentiation hypothesis. Additionally, histology revealed peribronchial inflammation and emphysema in wild-type mice after five weeks of allergen exposure, suggesting a role of ILC3s in emphysema development. Emphysema was also observed in Rag-KO mice, further supporting the involvement of ILCs in this process. These findings suggest chronic inflammation induces ILC2 dysfunction and transdifferentiation, possibly contributing to COPD in chronic asthma patients. Funding Sources This research was supported by CIHR Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)
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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 | 0.000 |
| 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".