ArticleBlood2013
TLR stimulation initiates a CD39-based autoregulatory mechanism that limits macrophage inflammatory responses.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
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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
88 citing papers in PubMed, 144 citations in OpenAlex.
- Neutrophil extracellular traps promote macrophage activation through Toll-like receptor engagement and PKA and NF-kB signaling pathways.Cell communication and signaling : CCS · 2026Article
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- Adenosine Pathway Activation Defines Genetically Linked Immunosuppressive Subtypes in Solid Tumor Brain Metastases.Cancers · 2026Article
- Exocytosed ATP as a therapeutic target for inflammatory and metabolic diseases.Frontiers in pharmacology · 2026Review
- Nucleotide Metabolic Reprogramming in Sepsis: From Immune-Cell Fate to Organ Injury and Precision Therapeutics.Journal of inflammation research · 2026Review
- Adipose tissue releases nucleosides.American journal of physiology. Cell physiology · 2026Article
- CD39 and CD73 Expression in Breast Cancer: CD73 as a Favorable Prognostic Factor in HER2-Positive Tumors.Journal of breast cancer · 2025Article
- Identification of purinergic system components in the venom of Bothrops mattogrossensis and the inhibitory effect of specioside extracted from Tabebuia aurea.Purinergic signalling · 2025Article
- Purinergic signaling in the battlefield of viral infections.Purinergic signalling · 2025Review
- Hsa-miR-342-3p and hsa-miR-360 may be the key molecules that promote periodontitis in type 2 diabetes mellitus.Heliyon · 2024Article
- Article
- Disruption of CD47-SIRPα signaling restores inflammatory function in tumor-associated myeloid-derived suppressor cells.iScience · 2024Article
- Upregulation of CD39 During Gout Attacks Promotes Spontaneous Remission of Acute Gouty Inflammation.Inflammation · 2024Article
- Platelet P2YBritish journal of pharmacology · 2024Review
- The interplay between the DNA damage response and ectonucleotidases modulates tumor response to therapy.Science immunology · 2023Review
- Corrigendum: Purinergic signaling systems across comparative models of spinal cord injury.Neural regeneration research · 2023Article
- The Role of Cluster of Differentiation 39 (CD39) and Purinergic Signaling Pathway in Viral Infections.Pathogens (Basel, Switzerland) · 2023Review
- Tumor Cell-derived Extracellular Vesicles in Modulating Phenotypes and Immune Functions of Macrophages: Mechanisms and Therapeutic Applications.Journal of Cancer · 2023Review
- The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury.Frontiers in immunology · 2023Review
- Prospective study and validation of early warning marker discovery based on integrating multi-omics analysis in severe burn patients with sepsis.Burns & trauma · 2023Article
28 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
6 authors at 5 institutions in 1 country.
Funding
Abstract
Sepsis is a highly fatal disease caused by an initial hyperinflammatory response followed by a state of profound immunosuppression. Although it is well appreciated that the initial production of proinflammatory cytokines by macrophages accompanies the onset of sepsis, it remains unclear what causes the transition to an immunosuppressive state. In this study, we reveal that macrophages themselves are key regulators of this transition and that the surface enzyme CD39 plays a critical role in self-limiting the activation process. We demonstrate that Toll-like receptor (TLR)-stimulated macrophages modulate their activation state by increasing the synthesis and secretion of adenosine triphosphate (ATP). This endogenous ATP is paradoxically immunosuppressive due to its rapid catabolism into adenosine by CD39. Macrophages lacking CD39 are unable to transition to a regulatory state and consequently continue to produce inflammatory cytokines. The importance of this transition is demonstrated in a mouse model of sepsis, where small numbers of CD39-deficient macrophages were sufficient to induce lethal endotoxic shock. Thus, these data implicate CD39 as a key "molecular switch" that allows macrophages to self-limit their activation state. We propose that therapeutics targeting the release and hydrolysis of ATP by macrophages may represent new ways to treat inflammatory diseases.
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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.