ArticleThe Journal of clinical investigation2021
PD-1 blockade improves Kupffer cell bacterial clearance in acute liver injury.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 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.
The trial behind it
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Who cites it
59 citing papers in PubMed, 104 citations in OpenAlex.
- Uncovering immune dysfunction in ACLF: Cellular mechanisms, molecular pathways, and therapeutic frontiers.Journal of hepatology · 2026Review
- Progressive Decline in Interferon-γ Release is Associated with Cirrhosis Progression and Severity: A Prospective Preliminary Report.Annals of laboratory medicine · 2026Article
- Kupffer cells in liver homeostasis and disease: from immune sentinels to metabolic gatekeepers.Nature reviews. Immunology · 2026Review
- Ripk2 promotes CD8Cell death & disease · 2026Article
- Identification and validation of key PANoptosis-related genes via integrative machine learning and single-cell sequencing in AILI.iScience · 2026Article
- PI3K/PKB signaling network as a host target to enhance bacterial ingestion and clearance.Biologia futura · 2026Review
- β-Glucan Protects Against Sepsis-Induced Kupffer Cell Loss by Inhibiting Pyroptosis and Promoting Self-Renewal.Immunology · 2026Article
- Biomimetic Polymer-Based Nanomaterials for Immune-Responsive Hepatocellular Carcinoma Therapy.International journal of nanomedicine · 2026Review
- The Dual Role of Natural Killer Cells in the Septic Liver.Journal of inflammation research · 2026Review
- Immunometabolic Reprogramming in Experimental Sepsis: A Driver of Multiple Organ Dysfunction Syndrome.Journal of inflammation research · 2026Review
- Drug-resistant bacterial infections in end-stage liver disease: immune imbalance and intervention advances.Frontiers in immunology · 2026Review
- The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025Review
- Emergence, function, and therapeutic strategies to target the PD-1/PD-L1 immune checkpoint during pathogenic fungal infections.Virulence · 2025Review
- T-2 Toxin Exploits Gut-Derived Staphylococcus Saprophyticus to Disrupt Hepatic Macrophage Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Myeloid cells in chronic liver inflammation.Cellular & molecular immunology · 2025Review
- Hepcidin sustains Kupffer cell immune defense against bloodstream bacterial infection via gut-derived metabolites in mice.The Journal of clinical investigation · 2025Article
- Kupffer Cells Regulate iNKT Cells Through Il-12 to Mitigate the Extent of APAP-Induced Damage in the Liver.Journal of cellular and molecular medicine · 2025Article
- Immune Dysfunction and Infection Risk in Advanced Liver Disease.Gastroenterology · 2025Review
- The role of heme in sepsis induced Kupffer cell PANoptosis and senescence.Cell death & disease · 2025Article
- eIF3a function in immunity and protection against severe sepsis by regulating B cell quantity and function through mActa pharmaceutica Sinica. B · 2025Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
Abstract
Patients with acute liver failure (ALF) have systemic innate immune suppression and increased susceptibility to infections. Programmed cell death 1 (PD-1) expression by macrophages has been associated with immune suppression during sepsis and cancer. We therefore examined the role of the programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) pathway in regulating Kupffer cell (KC) inflammatory and antimicrobial responses in acetaminophen-induced (APAP-induced) acute liver injury. Using intravital imaging and flow cytometry, we found impaired KC bacterial clearance and systemic bacterial dissemination in mice with liver injury. We detected increased PD-1 and PD-L1 expression in KCs and lymphocyte subsets, respectively, during injury resolution. Gene expression profiling of PD-1+ KCs revealed an immune-suppressive profile and reduced pathogen responses. Compared with WT mice, PD-1-deficient mice and anti-PD-1-treated mice with liver injury showed improved KC bacterial clearance, a reduced tissue bacterial load, and protection from sepsis. Blood samples from patients with ALF revealed enhanced PD-1 and PD-L1 expression by monocytes and lymphocytes, respectively, and that soluble PD-L1 plasma levels could predict outcomes and sepsis. PD-1 in vitro blockade restored monocyte functionality. Our study describes a role for the PD-1/PD-L1 axis in suppressing KC and monocyte antimicrobial responses after liver injury and identifies anti-PD-1 immunotherapy as a strategy to reduce infection susceptibility in ALF.
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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.