Connexin 43 Mediated Interaction Between Alveolar Macrophages and Type 2 Epithelial Progenitors Protects Against Bleomycin Induced Acute Lung Injury 3901
Bibliographic record
Abstract
Abstract Description Acute respiratory distress syndrome (ARDS) remains among the most common complications of critical illness. ARDS involves the death of type I alveolar epithelial cells, which are then repopulated by a progenitor subset of type II alveolar epithelial cell progenitors (AEP). All alveolar epithelial cell populations are in continuous contact with alveolar macrophages (AM), but the mechanistic role of AM in ARDS is undefined. We hypothesized that AM protect against ARDS through communication with AEPs. We generated mice with selective depletion of alveolar macrophages by deleting core-binding factor-β in the myeloid compartment (LysM-Cre+/- CBFβ-fl/fl). These animals were healthy at baseline but, in contrast to littermate controls, displayed progressive lung injury, inflammation, hypoxia, and death after bleomycin challenge. Mice with deletion of connexin-43 (Cx43) hemichannels in CD11c-expressing cells (CD11c-Cre+/- Cx43-fl/fl) displayed a similar susceptibility. AM expression of Cx43 was necessary to the susceptibility, because the phenotype was rescued by intrapulmonary adoptive transfer of wildtype AM but not the transfer of AM with deletion of Cx43 (from CD11c-Cre+/- Cx43-fl/fl donors). Finally, the phenotype was recapitulated in in mice deficient in Cx43 in AEP expressing Grainyhead transcription factor cellular promoter 2-like 1 (Tfc2l1-Cre+/- Cx43-fl/fl). In conclusion, AM protect against lung injury via a mechanism involving the Cx43 hemichannels on both AM and AEP. Funding Sources Supported by: NIH R01AI135128 and U01EB024501 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".