Anti-ST2 antibody reduces airway hyperresponsiveness mediated by monocyte-derived macrophages during influenza A infection
Bibliographic record
Abstract
Influenza A virus (IAV) infections trigger asthma attacks and cause airway hyperresponsiveness (AHR) in murine models. However, the mechanism by which AHR is induced remains to be fully elucidated. Here, we show that targeting the interleukin (IL)-33 suppression of tumorigenicity 2 (ST2) receptor complex with an anti-ST2 antibody during acute IAV infection of C57BL/6 mice reduced AHR, without affecting expansion of ILC2s and independently of IL-13. Among the lung inflammatory cells, the anti-ST2 antibody selectively reduced the monocyte-derived macrophages (MMs). Furthermore, AHR was reduced in C-C chemokine receptor 2 (CCR2)-knockout mice that have deficient MM recruitment. Depletion of MMs achieved by anti-Ly6C antibody administration also reduced AHR. The treatment of airway smooth muscle (ASM) with conditioned medium from IL-33-treated human THP-1-derived macrophages enhanced potassium chloride-induced ASM contraction. These findings suggest that MMs contribute to acute AHR following IAV infection in an IL-33-dependent manner, but independent of the ILC2/IL-13 axis. Additionally, IL-33 stimulates the release of macrophage-derived mediators that enhance airway smooth muscle contraction, offering a potential mechanistic basis for IAV-induced AHR.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".