AI Article Synopsis
Article Abstract
Objective: Immune paresis in patients with acute-on-chronic liver failure (ACLF) accounts for infection susceptibility and increased mortality. Immunosuppressive mononuclear CD14HLA-DR myeloid-derived suppressor cells (M-MDSCs) have recently been identified to quell antimicrobial responses in immune-mediated diseases. We sought to delineate the function and derivation of M-MDSC in patients with ACLF, and explore potential targets to augment antimicrobial responses.
Design: Patients with ACLF (n=41) were compared with healthy subjects (n=25) and patients with cirrhosis (n=22) or acute liver failure (n=30). CD14CD15CD11bHLA-DR cells were identified as per definition of M-MDSC and detailed immunophenotypic analyses were performed. Suppression of T cell activation was assessed by mixed lymphocyte reaction. Assessment of innate immune function included cytokine expression in response to Toll-like receptor (TLR-2, TLR-4 and TLR-9) stimulation and phagocytosis assays using flow cytometry and live cell imaging-based techniques.
Results: Circulating CD14CD15CD11bHLA-DR M-MDSCs were markedly expanded in patients with ACLF (55% of CD14+ cells). M-MDSC displayed immunosuppressive properties, significantly decreasing T cell proliferation (p=0.01), producing less tumour necrosis factor-alpha/interleukin-6 in response to TLR stimulation (all p<0.01), and reduced bacterial uptake of (p<0.001). Persistently low expression of HLA-DR during disease evolution was linked to secondary infection and 28-day mortality. Recurrent TLR-2 and TLR-4 stimulation expanded M-MDSC in vitro. By contrast, TLR-3 agonism reconstituted HLA-DR expression and innate immune function ex vivo.
Conclusion: Immunosuppressive CD14HLA-DR M-MDSCs are expanded in patients with ACLF. They were depicted by suppressing T cell function, attenuated antimicrobial innate immune responses, linked to secondary infection, disease severity and prognosis. TLR-3 agonism reversed M-MDSC expansion and innate immune function and merits further evaluation as potential immunotherapeutic agent.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969362 | PMC |
| http://dx.doi.org/10.1136/gutjnl-2017-314184 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Steatotic liver disease in metastatic breast cancer treated with endocrine therapy and CDK4/6 inhibitor.
Breast Cancer Res Treat
December 2024
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre University Health Network, 700 University Ave, Toronto, ON, M5G 1Z5, Canada.
Purpose: In early-stage breast cancer, steatotic liver disease (SLD) is associated with increased recurrence, cardiovascular events, and non-cancer death. Endocrine therapy (ET) increases the risk of SLD. The impact of cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) on SLD and prognostic association in metastatic breast cancer is unknown.
View Article and Find Full Text PDFAssociation between major depressive disorder or depressive symptoms and the risk of vascular complications among patients with type 2 diabetes, and the mediating role of metabolic biomarkers: an analysis of the UK Biobank cohort.
EClinicalMedicine
January 2025
Department of Epidemiology, NHC Key Laboratory for Health Technology Assessment, Fudan University School of Public Health, 138 Yi Xue Yuan Road, Shanghai, 200032, China.
Background: Depression is a severe mental disorder commonly co-morbid with diabetes, but it remains to elucidate whether depression is associated with the risks of a wide range of vascular complications in people with type 2 diabetes mellitus (T2DM) and whether metabolic biomarkers may mediate this pathway.
Methods: We conducted this prospective analysis among the participants of the UK Biobank who were diagnosed with T2DM and free of vascular complications at baseline between March 13, 2006 and September 30, 2010. Major depressive disorder (MDD) was ascertained according to the hospital admission records and self-report of doctor-diagnosed conditions, while the presence of depressive symptoms was assessed using the Patient Health Questionnaire-2.
Spontaneous Hepatic Rupture Complicating Preeclampsia and HELLP Syndrome: A Case Report.
Case Rep Med
December 2024
Department of Surgery, Jimma Medical Center, Jimma University, Jimma, Ethiopia.
Spontaneous hepatic rupture is a rare complication that occurs in pregnant mothers with HELLP syndrome, or preeclampsia with severe features, or eclampsia. The most common symptom of hepatic rupture/hematoma is right upper quadrant pain or epigastric pain, which is similar to the presentation of preeclampsia with severe features. Therefore, the absence of specific signs and symptoms leads to a diagnostic dilemma and a delay in management.
View Article and Find Full Text PDFThe Model for End-Stage Liver Disease (MELD) score is a widely used tool for quantifying hepatic dysfunction, providing greater accuracy and a wider range of values compared to the Child-Turcotte-Pugh (CTP) score, being also used in prioritizing patients who are eligible for liver transplantation. This study assessed the correlation between the MELD score and the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), a reliable system for categorizing risk levels in patients undergoing cardiovascular surgery. This retrospective study analyzed data from 589 patients who underwent coronary artery bypass grafting (CABG) at the Institute of Cardiovascular Diseases 'Prof.
View Article and Find Full Text PDFComparative study of transcriptomic alterations in sepsis-induced acute liver injury: Deciphering the role of alternative splicing in mouse models.
Int Immunopharmacol
December 2024
Department of Emergency, Kashi Prefecture Second People's Hospital, Uygur Autonomous Region Kashi, Xinjiang, 844000, China; Department of Emergency, Shanghai Tenth People's Hospital, School of Medicine Tongji University, Shanghai 200072, China. Electronic address:
Background: Sepsis represents a critical health crisis often leading to the failure of multiple organs, with the liver playing a pivotal role in controlling inflammation and defending against systemic infections. The exacerbation of liver damage can escalate sepsis severity, underscoring the necessity to delve into the molecular mechanisms underlying sepsis-induced acute liver injury (ALI). The role of alternative splicing (AS), a complex post-transcriptional mechanism, has been occasionally noted in relation to sepsis across different investigations.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!