ArticleThe Journal of biological chemistry2019
Lipopolysaccharide suppresses T cells by generating extracellular ATP that impairs their mitochondrial function via P2Y11 receptors.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Tracking spatio-temporal dynamics of early immune responses to an intranasal OMV-based pneumococcal vaccine candidate in mice.NPJ vaccines · 2026Article
- The Participation of Acetyl Phosphate, a Microbial and Host Metabolite, in the Regulation of the Calcium Balance in Mitochondria and Cells.International journal of molecular sciences · 2026Article
- Spatiotemporal transcriptomic profiling and modeling of mouse brain at single-cell resolution reveals cell proximity effects of aging and rejuvenation.bioRxiv : the preprint server for biology · 2024Article
- P2YPurinergic signalling · 2023Review
- Anti-Inflammatory Effects of Nutritionally Relevant Concentrations of Oleuropein and Hydroxytyrosol on Peripheral Blood Mononuclear Cells: An Age-Related Analysis.International journal of molecular sciences · 2023Article
- The Role of Cluster of Differentiation 39 (CD39) and Purinergic Signaling Pathway in Viral Infections.Pathogens (Basel, Switzerland) · 2023Review
- Who Knew? Dopamine Transporter Activity Is Critical in Innate and Adaptive Immune Responses.Cells · 2023Article
- Group B streptococci infection model shows decreased regulatory capacity of cord blood cells.Pediatric research · 2022Article
- P2X receptors in the balance between inflammation and pathogen control in sepsis.Purinergic signalling · 2022Article
- Dietary Supplementation of EGF Ameliorates the Negatively Effects of LPS on Early-Weaning Piglets: From Views of Growth Performance, Nutrient Digestibility, Microelement Absorption and Possible Mechanisms.Animals : an open access journal from MDPI · 2021Article
- Frontline Science: P2Y11 receptors support T cell activation by directing mitochondrial trafficking to the immune synapse.Journal of leukocyte biology · 2021Article
- Paramylon fromFrontiers in immunology · 2021Article
- The purinergic receptor P2Y11 choreographs the polarization, mitochondrial metabolism, and migration of T lymphocytes.Science signaling · 2020Article
- Signaling Through Purinergic Receptor P2YInternational journal of molecular sciences · 2020Article
- On the mechanism of anti-CD39 immune checkpoint therapy.Journal for immunotherapy of cancer · 2020Review
- Mitochondria Synergize With P2 Receptors to Regulate Human T Cell Function.Frontiers in immunology · 2020Review
- Targeting Purinergic Signaling in the Dynamics of Disease Progression in Sepsis.Frontiers in pharmacology · 2020Article
- Frontline Science: Escherichia coli use LPS as decoy to impair neutrophil chemotaxis and defeat antimicrobial host defense.Journal of leukocyte biology · 2019Article
- DAMPs and NETs in Sepsis.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
T cell suppression contributes to immune dysfunction in sepsis. However, the underlying mechanisms are not well-defined. Here, we show that exposure of human peripheral blood mononuclear cells to bacterial lipopolysaccharide (LPS) can rapidly and dose-dependently suppress interleukin-2 (IL-2) production and T cell proliferation. We also report that these effects depend on monocytes. LPS did not prevent the interaction of monocytes with T cells, nor did it induce programmed cell death protein 1 (PD-1) signaling that causes T cell suppression. Instead, we found that LPS stimulation of monocytes led to the accumulation of extracellular ATP that impaired mitochondrial function, cell migration, IL-2 production, and T cell proliferation. Mechanistically, LPS-induced ATP accumulation exerted these suppressive effects on T cells by activating the purinergic receptor P2Y11 on the cell surface of T cells. T cell functions could be partially restored by enzymatic removal of extracellular ATP or pharmacological blocking of P2Y11 receptors. Plasma samples obtained from sepsis patients had similar suppressive effects on T cells from healthy subjects. Our findings suggest that LPS and ATP accumulation in the circulation of sepsis patients suppresses T cells by promoting inappropriate P2Y11 receptor stimulation that impairs T cell metabolism and functions. We conclude that inhibition of LPS-induced ATP release, removal of excessive extracellular ATP, or P2Y11 receptor antagonists may be potential therapeutic strategies to prevent T cell suppression and restore host immune function in sepsis.
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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.