The club cell circadian clock regulates temporal patterns in leukocyte trafficking in chronic allergic airways disease
Bibliographic record
Abstract
Abstract Rationale Asthma displays temporally variable symptoms which worsen overnight, corresponding with a nocturnal increase in airway eosinophils. The molecular clock within the club cell of the bronchial epithelium is a key driver of lung rhythmic processes, however, it’s role in chronic allergic airways disease (AAD) is not known. Elucidating the role of the club cell clock in regulating rhythmic inflammation in AAD could lead to new therapeutic advances. Objectives To investigate the club cell molecular clock regulation of leukocyte trafficking in chronic AAD. Methods ccsp - bmal1 KO mice (which lack a functional clock in club cells) and littermate control mice underwent a 5-week chronic house dust mite (HDM) model of AAD, following which leukocyte populations and cytokines from blood, lung and airway compartments were quantified in a 24-hour time-course. Airway epithelial cells were cultured and transepithelial electrical resistance measured to explore circadian variability in barrier permeability and impact of pharmacological modulation of the clock. Main Results Leukocyte populations accumulate in the blood, lung and airways of HDM exposed mice in a time-of-day dependent manner, with time of peak accumulation dependent on cell type. This temporal gating of leukocyte accumulation is controlled and coordinated by the club cell circadian clock, which also regulates airway barrier integrity. Targeting REVERBa (a component of the molecular circadian clock), was effective at modifying airway barrier permeability achieving reduced transepithelial leukocyte migration. Conclusions The club cell clock gates leukocyte trafficking signals and airway barrier integrity by time of day in chronic allergic airway inflammation.
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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".