Hepatic macrophages and regulatory T cells (Tregs) play an important role in the maintenance of liver immune homeostasis, but the mechanism by which hepatic macrophages regulate Tregs in acute liver injury remains largely unknown. Here, we found that the hepatic Treg proportion and β-catenin expression in hepatic macrophages were associated with acetaminophen (APAP) and D-galactosamine (D-GalN)/ lipopolysaccharide (LPS)-induced acute liver injury. Interestingly, β-catenin was markedly upregulated only in infiltrating macrophages, but not in resident Kupffer cells. Myeloid-specific β-catenin knockout mice showed an increased inflammatory cell infiltration and hepatocyte apoptosis. Moreover, myeloid β-catenin deficiency decreased the hepatic Treg proportion in the injured liver. Mechanistically, in vitro co-culture experiments revealed that macrophage β-catenin modulated its exosome composition, and influenced Treg differentiation. Using mass spectrometry-based proteomics, we identified that macrophage β-catenin activation increased the level of exosomal α-SNAP, which in turn promoted Treg differentiation. Overall, our findings demonstrated a molecular mechanism that macrophage β-catenin regulated the Treg proportion in the liver by enhancing the expression of exosomal α-SNAP, providing insights into the pathophysiology of acute liver injury.
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http://dx.doi.org/10.1172/jci.insight.182515 | DOI Listing |
Med Clin (Barc)
December 2024
Servicio de Hepatología, Hospital Clínic de Barcelona, Barcelona, España; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, España; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Facultad de Medicina y Ciencias de la Salud, Universidad de Barcelona, Barcelona,, España. Electronic address:
Liver cirrhosis is a common cause of morbidity and mortality worldwide. Excessive alcohol consumption and metabolic associated steatotic liver disease are the most common etiological factors of cirrhosis in our region. Cirrhosis occurs in two well-differentiated phases, compensated and decompensated, depending on the absence or presence of complications, respectively.
View Article and Find Full Text PDFArch Cardiovasc Dis
December 2024
Department of Cardiology, CHU Montpellier, 34295 Montpellier, France.
Background: Recommended treatment after acute coronary syndrome (ACS) involves high-intensity statin therapy to achieve the low-density lipoprotein (LDL-C) target of<1.4mmol/L (European guidelines), but many patients discontinue statins because of real or perceived side-effects. Whether body mass index (BMI) influences statin intolerance remains unclear.
View Article and Find Full Text PDFMicrob Pathog
December 2024
Departamento de Biologia Animal (DBA), Programa de Pós-Graduação em Biologia Animal (PPGBA), Universidade Federal de Viçosa (UFV), Viçosa, 36570-900, Minas Gerais, Brazil.
Chronic inflammation, oxidative stress, and DNA damage are observed in schistosomiasis and premature aging. However, the potential of these events to trigger stress-induced premature senescence (SIPS) throughout schistosomiasis progression remains overlooked, especially in response to the first-line pharmacological treatment. Thus, we investigated the relationship between oxidative stress and SIPS sentinel markers in untreated Schistosoma mansoni-infected mice and those receiving praziquantel (Pz)-based reference treatment.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
December 2024
Department of Hepatobiliary Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China. Electronic address:
Liver transplantation is currently recognized as the most effective treatment for severe liver diseases. Although survival rates after liver transplantation have improved, rejection of the transplanted liver remains a significant cause of morbidity and transplant failure in patients. Our team previously discovered a close association between high GBP1 expression and acute rejection reactions following liver transplantation.
View Article and Find Full Text PDFJ Gastrointest Surg
December 2024
Department of Radiation Oncology, Institute of Liver and Biliary Sciences, Delhi, India. Electronic address:
Background: India has a high incidence of gallstones, which can cause chronic inflammation and increase the risk of gallbladder cancer. Understanding the age and composition of gallstones can provide insights into their formation and growth. This study used ¹⁴C dating, FTIR, and metagenome analysis to explore the natural history, deposition rate, and microbial/chemical composition of gallstones.
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