ArticlePLoS biology2015
Suppression of Dendritic Cell-Derived IL-12 by Endogenous Glucocorticoids Is Protective in LPS-Induced Sepsis.
Article in PLoS biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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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.
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Who cites it
68 citing papers in PubMed, 98 citations in OpenAlex.
- Balancing inflammation under stress: glucocorticoid regulation of innate immune pathways.Bioscience reports · 2026Review
- Dendritic-cell depletion and dysfunction in sepsis: a compartment- and evidence-aware synthesis.Frontiers in immunology · 2026Review
- Corticosteroids in sepsis.Journal of intensive medicine · 2025Review
- Urine metabolomic analyses reveal metabolite disruptions in steroid hormone biosynthesis in monkeypox.iScience · 2025Article
- CD40L-Activated DC Promotes Th17 Differentiation and Inhibits Th2 Differentiation in Sepsis-Induced Lung Injury via cGAS-STING Signaling.Biochemical genetics · 2025Article
- Chlorine gas poisoning by trichloroisocyanuric acid and respiratory failure: a case report of a 49-year-old patient.Frontiers in medicine · 2025Article
- Steroid hormone regulation of immunometabolism and inflammation.Frontiers in immunology · 2025Review
- The Role of SR-BI in sepsis: leveraging mechanistic insights to advance precision steroid therapy.Frontiers in immunology · 2025Review
- Glucocorticoid therapy for acute respiratory distress syndrome: Current concepts.Journal of intensive medicine · 2024Review
- Intestinal biofilms: pathophysiological relevance, host defense, and therapeutic opportunities.Clinical microbiology reviews · 2024Review
- Dysregulated dendritic cells in sepsis: functional impairment and regulated cell death.Cellular & molecular biology letters · 2024Review
- 2,4'-Dihydroxybenzophenone: A Promising Anti-Inflammatory Agent Targeting Toll-like Receptor 4/Myeloid Differentiation Factor 2-Mediated Mitochondrial Reactive Oxygen Species Production during Lipopolysaccharide-Induced Systemic Inflammation.ACS pharmacology & translational science · 2024Article
- Exploring the complex interplay: gut microbiome, stress, and leptospirosis.Frontiers in microbiology · 2024Review
- FOXO1-mediated autophagy regulation by miR-223 in sepsis-induced immunosuppression.Frontiers in pharmacology · 2024Article
- Local Effects of Steroid Hormones within the Bone Microenvironment.International journal of molecular sciences · 2023Review
- Modulating glucocorticoid receptor actions in physiology and pathology: Insights from coregulators.Pharmacology & therapeutics · 2023Review
- Effect of DMARDs on the immunogenicity of vaccines.Nature reviews. Rheumatology · 2023Review
- The Calm after the Storm: Implications of Sepsis Immunoparalysis on Host Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Genetic control of the dynamic transcriptional response to immune stimuli and glucocorticoids at single-cell resolution.Genome research · 2023Article
- Activation, Amplification, and Ablation as Dynamic Mechanisms of Dendritic Cell Maturation.Biology · 2023Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Sepsis, an exaggerated systemic inflammatory response, remains a major medical challenge. Both hyperinflammation and immunosuppression are implicated as causes of morbidity and mortality. Dendritic cell (DC) loss has been observed in septic patients and in experimental sepsis models, but the role of DCs in sepsis, and the mechanisms and significance of DC loss, are poorly understood. Here, we report that mice with selective deletion of the glucocorticoid receptor (GR) in DCs (GR(CD11c-cre)) were highly susceptible to LPS-induced septic shock, evidenced by elevated inflammatory cytokine production, hypothermia, and mortality. Neutralizing anti-IL-12 antibodies prevented hypothermia and death, demonstrating that endogenous GC-mediated suppression of IL-12 is protective. In LPS-challenged GR(CD11c-cre) mice, CD8(+) DCs were identified as the major source of prolonged IL-12 production, which correlated with elevations of NK cell-derived IFN-γ. In addition, the loss of GR in CD11c(+) cells rescued LPS-induced loss of CD8(+) DCs but not other DC subsets. Unlike wild-type animals, exposure of GR(CD11c-cre) mice to low-dose LPS did not induce CD8(+) DC loss or tolerance to subsequent challenge with high dose, but neutralization of IL-12 restored the ability of low-dose LPS to tolerize. Therefore, endogenous glucocorticoids blunt LPS-induced inflammation and promote tolerance by suppressing DC IL-12 production.
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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.