Signalling<i>via</i>CD131 regulates pulmonary inflammation, alveolar cell death and emphysema in COPD
Bibliographic record
Abstract
Background: COPD is a heterogenous disease where chronic inflammation is implicated in airway remodelling and emphysema. The CD131 receptor is indispensable for signalling by the β common (βc) family of cytokines encompassing granulocyte-macrophage colony-stimulating factor, interleukin (IL)-5 and IL-3, which instigate both type-2 and non-type-2 inflammatory responses. This study aims to determine whether antagonising CD131 signalling can prevent pulmonary inflammation, alveolar cell death and emphysema development. Methods: ) and pathway enrichment for βc cytokine signalling in blood, sputum and lung biopsies of COPD patients. To model emphysema, transgenic mice expressing human CD131 were exposed to elastase or cigarette smoke (CS) and a fully human monoclonal antibody (CSL311) was employed to inhibit CD131 signalling. Results: CD131 gene expression was significantly increased in COPD, along with an enrichment of gene set for βc cytokine signalling. In transgenic mice subjected to emphysema models, CD131 antagonism effectively prevented lung injury, alveolar cell death and emphysema development. Mechanistically, RNA sequencing identified pathway enrichment for myeloid cell activation, type-2 immune response and macrophage alternative activation in elastase-induced emphysematous mice, mirroring human COPD. Blocking CD131 signalling almost completely reversed the global gene expression alterations associated with emphysema development. Conclusions: CD131 signalling orchestrates pulmonary inflammation in COPD, resulting in immunopathology that underpins emphysema and lung function decline. Antagonising CD131 therefore represents a unique strategy to simultaneously target multiple pathogenic myeloid cell populations.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".