ArticleCell reports2018
The Circadian Clock Controls Immune Checkpoint Pathway in Sepsis.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
109 citing papers in PubMed, 163 citations in OpenAlex.
- Targeting the NR1D1-IGF2BP2-V-ATPase Axis With Hybrid Nanovesicles Restores Macrophage Rhythms to Reverse Sepsis-Induced Immunosuppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Arntl deficiency impairs NK cell function by reducing responsiveness to IL-15 and suppressing activation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Circadian Rhythms in Acute Respiratory Distress Syndrome: Molecular Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Histone Lactylation in Immune Cells and Its Predictive Role in Sepsis Progression: A Prospective Observational Study.Shock (Augusta, Ga.) · 2026Observational
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Temporal dynamics in cancer immunotherapy: the interplay between circadian rhythms, tumor microenvironment, and immune checkpoint blockade.Journal of the National Cancer Center · 2026Review
- Circadian rhythm in immunotherapy and cellular therapy: impacts on the tumor microenvironment.Acta biochimica et biophysica Sinica · 2026Review
- Immunometabolic control of macrophage plasticity in wound healing: mechanistic insights and therapeutic opportunities.Frontiers in immunology · 2026Review
- BMAL1 alleviates sepsis-induced acute kidney injury by inhibiting apoptosis, ferroptosis and inflammation.Hereditas · 2025Article
- The βScience advances · 2025Article
- Heat stress affects expression levels of circadian clock gene Bmal1 and cyclins in rat thoracic aortic endothelial cells.Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Macrophage clock of pregnancy: circadian and metabolic control of decidual macrophage.Seminars in immunopathology · 2025Review
- Exploring ENPP5 as a diagnostic biomarker for sepsis: a comprehensive bioinformatics analysis.BMC infectious diseases · 2025Article
- A neuroimmune pathway drives bacterial infection.Science advances · 2025Article
- Roles of circadian clocks in macrophage metabolism: implications in inflammation and metabolism of lipids, glucose, and amino acids.American journal of physiology. Endocrinology and metabolism · 2025Review
- Circadian metabolic adaptations to infections.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Basic helix-loop-helix ARNT like 1 regulates the function of immune cells and participates in the development of immune-related diseases.Burns & trauma · 2025Review
- Circadian rhythm in mycotoxin-induced immunotoxicity: an emerging regulatory axis?Frontiers in pharmacology · 2025Review
- Circadian immune system in solid organ transplantation: a review article.Frontiers in immunology · 2025Review
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Sepsis and septic shock are associated with life-threatening organ dysfunction caused by an impaired host response to infections. Although circadian clock disturbance impairs the early inflammatory response, its impact on post-septic immunosuppression remains poorly elucidated. Here, we show that Bmal1, a core circadian clock gene, plays a role in the regulation of host immune responses in experimental sepsis. Mechanistically, Bmal1 deficiency in macrophages increases PKM2 expression and lactate production, which is required for expression of the immune checkpoint protein PD-L1 in a STAT1-dependent manner. Consequently, targeted ablation of Pkm2 in myeloid cells or administration of anti-PD-L1-neutralizing antibody or supplementation with recombinant interleukin-7 (IL-7) facilitates microbial clearance, inhibits T cell apoptosis, reduces multiple organ dysfunction, and reduces septic death in Bmal1-deficient mice. Collectively, these findings suggest that the circadian clock controls the immune checkpoint pathway in macrophages and therefore represents a potential therapeutic target for lethal 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.