STAT6-IP–Dependent Disruption of IL-33–Mediated ILC2 Expansion and Type 2 Innate Immunity in the Murine Lung
Bibliographic record
Abstract
Recent interest has focused on innate-type cytokines as promoters of type 2 immunity and targets for drug development in asthma. IL-33 induces production of IL-4 and/or IL-13, which is associated with STAT6-dependent responses in innate cells, including group 2 innate lymphoid cells (ILC2s), macrophages, and eosinophils. Our published data show that STAT6-immunomodulatory peptide (STAT6-IP), an immunomodulatory peptide designed to inhibit the STAT6 transcription factor, reduces induction of Th2 adaptive immunity in respiratory syncytial virus infection and asthma models. Nevertheless, the mechanism of STAT6-IP-dependent inhibition has remained obscure. In this study, we demonstrate that STAT6-IP reduced IL-33-induced type 2 innate lung inflammation. Specifically, our data show that STAT6-IP reduced recruitment and activation of eosinophils as well as polarization of alternatively activated macrophages. Decreases in these cells correlated with reduced levels of IL-5 and IL-13 as well as several type 2 chemokines in the bronchoalveolar lavage fluid. STAT6-IP effectively inhibited expansion of ILC2s as well as the number of IL-5- and IL-13-producing ILC2s. Our data suggest that STAT6-IP effectively disrupts IL-13-dependent positive feedback loops, initiated by ILC2 activation, to suppress IL-33-induced type 2 innate immunity in the murine lung.
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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 | 0.002 | 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".