Nerve associated lung resident interstitial macrophage subset exhibits distinct localization and polarization
Bibliographic record
Abstract
Abstract Tissue resident macrophages are a diverse population of cells that perform specialized functions: sustaining tissue homeostasis and tissue surveillance. Here we report an interstitial subset of CD169+ lung resident macrophages that are transcriptionally and developmentally distinct from alveolar macrophages (AM). They are primarily localized around the airways and in close contact with the innervating pulmonary nerves. These nerve and airway associated macrophages (NAMs) are tissue resident, yolk sac derived, self-renewing, and do not require CCR2+ monocytes for development or maintenance. We show that unlike AMs, CSF-1, but not CSF-2 is required for their development. Bulk population and single cell transcriptome analysis indicates that NAMs are distinct from other lung resident macrophage subsets and highly expressed immune regulatory genes under steady state and inflammatory conditions. NAMs proliferated robustly following TLR activation and influenza infection, and in their absence, the inflammatory response was remarkably augmented resulting in excessive production of inflammatory cytokines and innate immune cell infiltration. We show that AMs contribute to viral clearance while NAMs, contribute to regulating virus-induced inflammation in the lung. Overall, our study relates structure to function at a fundamental level, and provides essential insights into a distinct subset of resident macrophages in the lung that function to maintain immune and tissue homeostasis.
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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".