Neutrophil subsets in noncancer liver diseases: Cellular crosstalk and therapeutic targets

Neutrophils are the most abundant circulating granulocytes, linking innate and adaptive immunity. Neutrophils can regulate inflammatory and immune responses through degranulation, reactive oxygen species generation, the production of cytokines and chemokines, and NETosis. Emerging evidence has indicated that neutrophils contribute to the pathogenesis of various noncancer liver diseases, including nonalcoholic fatty liver disease, alcohol‐associated liver disease, hepatic ischemia‒reperfusion injury, and liver fibrosis. Cellular interactions among neutrophils, other immune cells, and nonimmune cells constitute a complex network that regulates the immune microenvironment of the liver. This review summarizes novel neutrophil subtypes, including CD177+ neutrophils and low‐density neutrophils. Moreover, we provide an overview of the cellular cros stalk of neutrophils in noncancer liver diseases, aiming to shed new light on mechanistic studies of novel neutrophil subtypes. In addition, we discuss the potential of neutrophils as therapeutic targets in noncancer liver diseases, including inhibitors targeting NETosis, granule proteins, and chemokines.

• Publication year

  2023

• Venue

  European Journal of Immunology

• Publication date

  2023-07-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1002/eji.202250324PMID 37495829
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• CD177 Inhibits Neutrophil Extracellular Trap Formation and Protects against Acute Pancreatitis in Mice

  2023cited by this paper
• The Role of Neutrophils as a Driver in Hepatic Ischemia-Reperfusion Injury and Cancer Growth

  2022cited by this paper
• Neutrophil Extracellular Traps Mediate Acute Liver Failure in Regulation of miR-223/Neutrophil Elastase Signaling in Mice

  2022cited by this paper
• Indicator of Inflammation and NETosis—Low-Density Granulocytes as a Biomarker of Autoimmune Hepatitis

  2022cited by this paper
• Mechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo.

  2022cited by this paper
• Peripheral γδ T Cells Regulate Neutrophil Expansion and Recruitment in Experimental Psoriatic Arthritis

  2022cited by this paper
• CXCR2 inhibition enables NASH-HCC immunotherapy

  2022cited by this paper
• Neutrophils in chronic inflammatory diseases

  2022cited by this paper
• Neutrophil extracellular traps and their histones promote Th17 cell differentiation directly via TLR2

  2022cited by this paper
• Competitively disrupting the neutrophil-specific receptor–autoantigen CD177:proteinase 3 membrane complex reduces anti-PR3 antibody-induced neutrophil activation

  2022cited by this paper
• Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease

  2022cited by this paper
• Cellular and transcriptional dynamics of human neutrophils at steady state and upon stress

  2022cited by this paper
• Neutrophil extracellular traps contribute to liver damage and increase defective low-density neutrophils in alcoholic hepatitis.

  2022cited by this paper
• CD177+ cells produce neutrophil extracellular traps to promote biliary atresia.

  2022cited by this paper
• Tumor-associated neutrophils and neutrophil-targeted cancer therapies.

  2022cited by this paper
• Liver-specific T regulatory type-1 cells program local neutrophils to suppress hepatic autoimmunity via CRAMP.

  2021cited by this paper
• Cross-Talk among Polymorphonuclear Neutrophils, Immune, and Non-Immune Cells via Released Cytokines, Granule Proteins, Microvesicles, and Neutrophil Extracellular Trap Formation: A Novel Concept of Biology and Pathobiology for Neutrophils

  2021cited by this paper
• Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner

  2021cited by this paper
• MicroRNA-223 restricts liver fibrosis by inhibiting the TAZ-IHH-GLI2 and PDGF signaling pathways via the crosstalk of multiple liver cell types

  2021cited by this paper
• Role of liver sinusoidal endothelial cells in liver diseases

  2021cited by this paper
• Anserine, HClO-scavenger, protected against cognitive decline in individuals with mild cognitive impairment

  2021cited by this paper
• Studying Neutrophil Function in vitro: Cell Models and Environmental Factors

  2021cited by this paper
• Liver ischaemia–reperfusion injury: a new understanding of the role of innate immunity

  2021cited by this paper
• Neutrophil extracellular traps: from physiology to pathology.

  2021cited by this paper
• Inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD177

  2021cited by this paper
• Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens

  2021cited by this paper
• E-Selectin-Dependent Inflammation and Lipolysis in Adipose Tissue Exacerbate Steatosis-to-NASH Progression via S100A8/9

  2021cited by this paper
• Regulatory T cell and neutrophil extracellular trap interaction contributes to carcinogenesis in non-alcoholic steatohepatitis.

  2021cited by this paper
• Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis

  2021cited by this paper
• Tetramethylpyrazine inhibits neutrophil extracellular traps formation and alleviates hepatic ischemia/reperfusion injury in rat liver transplantation.

  2021cited by this paper
• The Neutrophil.

  2021cited by this paper
• CD177, a specific marker of neutrophil activation, is associated with coronavirus disease 2019 severity and death

  2021cited by this paper
• A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients

  2021cited by this paper
• RNA Externalized by Neutrophil Extracellular Traps Promotes Inflammatory Pathways in Endothelial Cells

  2021cited by this paper
• Cholesterol-Induced M4-Like Macrophages Recruit Neutrophils and Induce NETosis

  2021cited by this paper
• Neutrophil extracellular traps induced by pro-inflammatory cytokines enhance procoagulant activity in NASH patients.

  2021cited by this paper
• CXCR1 and CXCR2 Inhibition by Ladarixin Improves Neutrophil-Dependent Airway Inflammation in Mice

  2020cited by this paper
• Single dose escalation studies with inhaled POL6014, a potent novel selective reversible inhibitor of human neutrophil elastase, in healthy volunteers and subjects with cystic fibrosis.

  2020cited by this paper
• NAFLD 2020: The State of the Disease.

  2020cited by this paper
• On the origin of low‐density neutrophils

  2020cited by this paper
• CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity.

  2020cited by this paper
• The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure

  2020cited by this paper
• Acetyl-CoA carboxylase inhibition disrupts metabolic reprogramming during hepatic stellate cell activation.

  2020cited by this paper
• Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds

  2020cited by this paper
• Protective and Detrimental Roles of p38α Mitogen‐Activated Protein Kinase in Different Stages of Nonalcoholic Fatty Liver Disease

  2020cited by this paper
• DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25

  2020cited by this paper
• Low‐Density Neutrophils in Systemic Lupus Erythematosus

  2020cited by this paper
• CXCR2 antagonist for patients with chronic obstructive pulmonary disease with chronic mucus hypersecretion: a phase 2b trial

  2020cited by this paper
• Chronic-plus-binge alcohol intake induces production of proinflammatory mtDNA-enriched extracellular vesicles and steatohepatitis via ASK1-p38MAPKα-dependent mechanisms.

  2020cited by this paper
• Cellular Mechanisms of NETosis.

  2020cited by this paper
• A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics

  2020cited by this paper
• Early Clinical Experience With AZD4831, A Novel Myeloperoxidase Inhibitor, Developed for Patients With Heart Failure With Preserved Ejection Fraction

  2020cited by this paper
• AAV‐mediated gene transfer of DNase I in the liver of mice with colorectal cancer reduces liver metastasis and restores local innate and adaptive immune response

  2020cited by this paper
• The role of neutrophils in innate immunity-driven nonalcoholic steatohepatitis: lessons learned and future promise

  2020cited by this paper
• Netting Liver Disease: Neutrophil Extracellular Traps in the Initiation and Exacerbation of Liver Pathology

  2020cited by this paper
• Exercise Training Decreases Hepatic Injury and Metastases Through Changes in Immune Response to Liver Ischemia/Reperfusion in Mice

  2020cited by this paper
• Therapeutic Targeting of Myeloperoxidase Attenuates NASH in Mice

  2020cited by this paper
• Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

  2020cited by this paper
• Bioinspired DNase‐I‐Coated Melanin‐Like Nanospheres for Modulation of Infection‐Associated NETosis Dysregulation

  2020cited by this paper
• Neutrophils in liver diseases: pathogenesis and therapeutic targets

  2020cited by this paper
• Neutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis

  2020cited by this paper
• Histidine‐Rich Glycoprotein Alleviates Liver Ischemia/Reperfusion Injury in Mice With Nonalcoholic Steatohepatitis

  2020cited by this paper
• Neutrophil-to-hepatocyte communication via LDLR-dependent miR-223-enriched extracellular vesicle transfer ameliorates nonalcoholic steatohepatitis.

  2020cited by this paper
• Two Faces of Neutrophils in Liver Disease Development and Progression

  2020cited by this paper
• Neutrophil extracellular traps promote fibrous vascular occlusions in chronic thrombosis.

  2020cited by this paper
• Neutrophils contribute to spontaneous resolution of liver inflammation and fibrosis via microRNA-223.

  2019cited by this paper
• Dipeptidase-1 Is an Adhesion Receptor for Neutrophil Recruitment in Lungs and Liver.

  2019cited by this paper
• Interleukin‐22 Ameliorates Neutrophil‐Driven Nonalcoholic Steatohepatitis Through Multiple Targets

  2019cited by this paper
• Knockout of neutrophil elastase protects against western diet induced nonalcoholic steatohepatitis in mice by regulating hepatic ceramides metabolism.

  2019cited by this paper
• Neutrophil Heterogeneity as Therapeutic Opportunity in Immune-Mediated Disease

  2019cited by this paper
• Neutrophil Cathepsin G Regulates Dendritic Cell Production of IL-12 during Development of CD4 T Cell Responses to Antigens in the Skin

  2019cited by this paper
• Deletion of C-C Motif Chemokine Ligand 5 Worsens Invariant Natural Killer T-Cell–Mediated Hepatitis via Compensatory Up-regulation of CXCR2–Related Chemokine Activity

  2019cited by this paper
• Neutrophils promote the development of reparative macrophages mediated by ROS to orchestrate liver repair

  2019cited by this paper
• The Neutrophil's Role During Health and Disease.

  2019cited by this paper
• Mechanical Stretch Increases Expression of CXCL1 in Liver Sinusoidal Endothelial Cells to Recruit Neutrophils, Generate Sinusoidal Microthombi, and Promote Portal Hypertension.

  2019cited by this paper
• Neutrophil plasticity in the tumor microenvironment.

  2019cited by this paper
• Safety and efficacy of the human neutrophil elastase inhibitor BAY 85-8501 for the treatment of non-cystic fibrosis bronchiectasis: A randomized controlled trial.

  2019cited by this paper
• Neutrophil Extracellular Traps Confine Pseudomonas aeruginosa Ocular Biofilms and Restrict Brain Invasion.

  2019cited by this paper
• Staphylococcus aureus drives expansion of low-density neutrophils in diabetic mice.

  2019cited by this paper
• Biological Roles of Neutrophil-Derived Granule Proteins and Cytokines.

  2019cited by this paper
• Neutrophil Diversity in Health and Disease

  2019cited by this paper
• Neutrophil Extracellular Traps Induce Intestinal Damage and Thrombotic Tendency in Inflammatory Bowel Disease.

  2019cited by this paper
• Advanced Glycated End Products Alter Neutrophil Effect on Regulation of CD4+ T Cell Differentiation Through Induction of Myeloperoxidase and Neutrophil Elastase Activities

  2018cited by this paper
• Neutrophil extracellular traps promote inflammation and development of hepatocellular carcinoma in nonalcoholic steatohepatitis

  2018cited by this paper
• Hepatocytes and neutrophils cooperatively suppress bacterial infection by differentially regulating lipocalin‐2 and neutrophil extracellular traps

  2018cited by this paper
• Neutrophil–Hepatic Stellate Cell Interactions Promote Fibrosis in Experimental Steatohepatitis

  2018cited by this paper
• Neutrophils and neutrophil extracellular traps in the liver and gastrointestinal system

  2018cited by this paper
• Ductular Reaction Cells Display an Inflammatory Profile and Recruit Neutrophils in Alcoholic Hepatitis

  2018cited by this paper
• The Role of Neonatal Gr-1+ Myeloid Cells in a Murine Model of Rhesus-Rotavirus-Induced Biliary Atresia.

  2018cited by this paper
• Effect of the CXCR2 antagonist danirixin on symptoms and health status in COPD

  2018cited by this paper
• Neutrophil Extracellular Traps Induce Endothelial Cell Activation and Tissue Factor Production Through Interleukin-1&agr; and Cathepsin G

  2018cited by this paper
• Abnormal neutrophil traps and impaired efferocytosis contribute to liver injury and sepsis severity after binge alcohol use.

  2018cited by this paper
• CD177+ neutrophils suppress epithelial cell tumourigenesis in colitis-associated cancer and predict good prognosis in colorectal cancer

  2018cited by this paper
• Neutrophil Elastase Inhibitors and Chronic Kidney Disease

  2018cited by this paper
• Mitochondrial DNA-enriched microparticles promote acute-on-chronic alcoholic neutrophilia and hepatotoxicity.

  2017cited by this paper
• Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice

  2017cited by this paper
• CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation.

  2017cited by this paper
• NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice.

  2017cited by this paper
• CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD

  2017cited by this paper
• IL-33 exacerbates liver sterile inflammation by amplifying neutrophil extracellular trap formation.

  2017cited by this paper

• The Role of Neutrophils in Non-Alcoholic Fatty Liver Disease: Mechanisms and Clinical Significance

  2026cites this paper
• Potential association of neutrophil-albumin ratio with non-alcoholic fatty liver disease: A cross-sectional study based on NHANES

  2025cites this paper
• Association between neutrophil-albumin ratio and ultrasound-defined metabolic dysfunction-associated fatty liver disease in U.S. adults: evidence from NHANES 2017–2018

  2025cites this paper
• Neutrophil extracellular traps (NETs) and NETosis in alcohol-associated diseases: A systematic review.

  2025cites this paper
• Neutrophil extracellular traps mediate pathophysiology of hepatic cells during liver injury

  2025cites this paper
• Temporal dichotomy of neutrophil function in acute liver injury and repair

  2025cites this paper
• The Roles of Neutrophil Cells in the Pathogenesis of Fibrosis: Mechanisms for Disease Progression

  2025influential citation
• Interactions between hepatic stellate cells and immune cells: Implications for liver fibrosis.

  2025cites this paper
• Granulocyte colony‐stimulating factor induced T‐cell hyporesponsiveness via modulation of CD177+S100Ahi neutrophils in unexplained recurrent pregnancy loss

  2025cites this paper
• Circulating Neutrophil Profiles Undergo a Dynamic Shift during Metabolic Dysfunction-Associated Steatohepatitis (MASH) Progression

  2024cites this paper
• Role of immune cell interactions in alcohol-associated liver diseases

  2024cites this paper
• Neutrophil PAD4 Expression and Its Pivotal Role in Assessment of Alcohol-Related Liver Disease

  2024cites this paper
• Proceedings of the 5th Meeting of Translational Hepatology, organized by the Spanish Association for the Study of the Liver (AEEH)

  2024cites this paper
• Machine Learning and Experimental Validation Identified Ferroptosis Signature and Innovative Biomarkers (ESR1 and GSTZ1) in Liver Fibrosis

  2024cites this paper
• aProceedings of the 5th Meeting of Translational Hepatology, organized by the Spanish Association for the Study of the Liver (AEEH).

  2024cites this paper
• Photodynamic Therapy and Adaptive Immunity Induced by Reactive Oxygen Species: Recent Reports

  2024cites this paper