ArticleNature medicine2014
An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 290 papers, 1 of them a synthesis that pooled it.
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Who cites it
290 citing papers in PubMed, 1 synthesis or guideline pooled it, 446 citations in OpenAlex.
- Circadian Variation in the Response to Vaccination: A Systematic Review and Evidence Appraisal.Journal of biological rhythms · 2024Pooled it
- BMAL1 Overexpression in the SCN Confers Protection Against Anxiety-Like Behaviors of Chronic Sleep Restricted-Mice.Molecular neurobiology · 2026Article
- The club cell circadian clock regulates temporal patterns in leukocyte trafficking in chronic allergic airways disease.Mucosal immunology · 2026Article
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Circadian Disruption Exacerbates Innate Immune Responses by Modulating the Bistability of Pro-Inflammatory Signaling: A Dynamical Modeling Study.Biomedicines · 2026Article
- Time-series single-cell transcriptomics reveals pervasive daily rhythmicity and nocturnal spermatogenesis in the zebrafish testis.Science advances · 2026Article
- Review
- Cryptochrome Loss Drives COPD-like Lung Pathology through Disrupted Alveolar Epithelial Proliferation and Immune Homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Circadian Rhythms in Acute Respiratory Distress Syndrome: Molecular Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Adrenaline restores Bmal1 transcriptional rhythms dampened by SARS-CoV-2 infection in Cthrc1-positive pulmonary fibroblasts derived from the Nile grass rat.Scientific reports · 2026Article
- Circadian rhythm and the molecular clock in endothelial function of the cardiovascular system.Molecular and cellular biochemistry · 2026Review
- RelA Signaling inInternational journal of molecular sciences · 2026Article
- Time of day alters olfactory bulb immune state with ramifications for intranasal inflammatory challenge.Cell reports · 2026Article
- By dawn or dusk-how circadian timing rewrites bacterial infection outcomes.FEBS letters · 2026Review
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Evolutionary Integration and Glucocorticoid Regulation of the Respiratory System: Structure, Function, and Homeostatic Adaptation.Medical sciences (Basel, Switzerland) · 2026Review
- A circadian checkpoint relocates neutrophils to minimize injury.The Journal of experimental medicine · 2026Article
- Temporal dynamics in cancer immunotherapy: the interplay between circadian rhythms, tumor microenvironment, and immune checkpoint blockade.Journal of the National Cancer Center · 2026Review
- Role of IL-10 signaling in the circadian control of host response to influenza infection.Mucosal immunology · 2026Article
- Circadian fluctuation of soluble CD26 dictates the impact of the timing of cord blood transplantation on acute graft-versus-host disease.Nature communications · 2026Article
230 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
The circadian system is an important regulator of immune function. Human inflammatory lung diseases frequently show time-of-day variation in symptom severity and lung function, but the mechanisms and cell types underlying these effects remain unclear. We show that pulmonary antibacterial responses are modulated by a circadian clock within epithelial club (Clara) cells. These drive circadian neutrophil recruitment to the lung via the chemokine CXCL5. Genetic ablation of the clock gene Bmal1 (also called Arntl or MOP3) in bronchiolar cells disrupts rhythmic Cxcl5 expression, resulting in exaggerated inflammatory responses to lipopolysaccharide and an impaired host response to Streptococcus pneumoniae infection. Adrenalectomy blocks rhythmic inflammatory responses and the circadian regulation of CXCL5, suggesting a key role for the adrenal axis in driving CXCL5 expression and pulmonary neutrophil recruitment. Glucocorticoid receptor occupancy at the Cxcl5 locus shows circadian oscillations, but this is disrupted in mice with bronchiole-specific ablation of Bmal1, leading to enhanced CXCL5 expression despite normal corticosteroid secretion. The therapeutic effects of the synthetic glucocorticoid dexamethasone depend on intact clock function in the airway. We now define a regulatory mechanism that links the circadian clock and glucocorticoid hormones to control both time-of-day variation and the magnitude of pulmonary inflammation and responses to bacterial infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.