ArticleAmerican journal of respiratory and critical care medicine2008
CD40 and CD80/86 act synergistically to regulate inflammation and mortality in polymicrobial sepsis.
Article in American journal of respiratory and critical care medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 99 citations in OpenAlex.
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- TheBioMed research international · 2018Trial
- Novel genetic insights into causal effects of potential metformin targets and immune mediation on sepsis.Biology direct · 2026Article
- Organ-specific inflammatory profiles during sepsis: divergent macrophage polarization and oxidative stress response in lung and liver in mouse model of caecal ligation and puncture.Journal of inflammation (London, England) · 2026Article
- Lung Dysfunction and Systemic Inflammation: A Role for HO-1 and NLRP3 in a COVID-19 Murine Model.Research square · 2026Article
- Co-culture of bone marrow-derived macrophages with aged primary myoblasts.Biology methods & protocols · 2026Article
- Protective Effects of a Dihydrodiazepine Against Endotoxin Shock Through Suppression of TLR4/NF-κB/IRF3 Signaling Pathways.Inflammation · 2025Article
- CD40L-Activated DC Promotes Th17 Differentiation and Inhibits Th2 Differentiation in Sepsis-Induced Lung Injury via cGAS-STING Signaling.Biochemical genetics · 2025Article
- Presence of CD80 and Absence of LAT in Modulating Cellular Infiltration and HSV-1 Latency.Viruses · 2024Article
- Controlled production of lipopolysaccharides increases immune activation in Salmonella treatments of cancer.Microbial biotechnology · 2024Article
- CD8Frontiers in immunology · 2024Article
- SOCS1 regulates a subset of NFκB-target genes through direct chromatin binding and defines macrophage functional phenotypes.iScience · 2023Article
- Pneumonia in the first week after polytrauma is associated with reduced blood levels of soluble herpes virus entry mediator.Frontiers in immunology · 2023Article
- Mass cytometry and single-cell RNA sequencing reveal immune cell characteristics of active and inactive phases of Crohn's disease.Frontiers in medicine · 2022Article
- HDAC Inhibition as Potential Therapeutic Strategy to Restore the Deregulated Immune Response in Severe COVID-19.Frontiers in immunology · 2022Article
- Molecular and Clinical Characterization of CD80 ExpressionFrontiers in pharmacology · 2022Article
- Point-of-critical-care diagnostics for sepsis enabled by multiplexed micro and nanosensing technologies.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2021Review
- IL-1β primed mesenchymal stromal cells moderate hemorrhagic shock-induced organ injuries.Stem cell research & therapy · 2021Article
- Encephalitozoon cuniculi takes advantage of efferocytosis to evade the immune response.PloS one · 2021Article
- CD28 Agonism Improves Survival in Immunologically Experienced Septic Mice via IL-10 Released by Foxp3Journal of immunology (Baltimore, Md. : 1950) · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleCostimulatory molecules, including the CD40-CD154 and CD80/86-CD28 dyads, play a prominent role in regulating inflammation in the adaptive immune response. Studies from our group and others suggest a potentially important role for these costimulatory cascades in innate immunity as well.
objectivesTo determine the role of CD80/86 alone and in combination with CD40 in lethal polymicrobial sepsis in mice and humans.
methodsThe murine cecal ligation and puncture (CLP) model was used to determine the role of CD80/86 alone and in combination with CD40 using wild-type mice, CD80/86(-/-) mice, and novel CD40/80/86(-/-) mice. Expression of cell-bound and soluble costimulatory molecules was assessed in humans via ELISA and flow cytometry. MEASUREMENTS AND MAIN
resultsLethal CLP was associated with up-regulation of CD40 and CD80/86 and their respective ligands CD28 and CD154 on innate effector cells. Blockade or deletion of CD80/86 attenuated mortality and inflammatory cytokine production during CLP. CD40/80/86(-/-) mice exhibited further reductions in mortality, lung injury, and inflammatory cytokine production compared with CD80/86(-/-) mice. Finally, humans with sepsis had increased monocyte expression of CD40 and CD80 compared with healthy control subjects; with higher levels in subjects requiring vasopressor support. Levels of soluble CD28 and CD154 were significantly higher in patients who died compared with those who lived.
conclusionsThese data demonstrate a central role for CD40 and CD80/86 in the innate immune response and suggest that combined inhibition of CD40 and CD80/86 may improve mortality in sepsis. Expression of costimulatory molecules may serve as biomarkers for outcome in septic patients.
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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.