Intrahepatic macrophage populations in the pathophysiology of primary sclerosing cholangitis

التفاصيل البيبلوغرافية
العنوان: Intrahepatic macrophage populations in the pathophysiology of primary sclerosing cholangitis
المؤلفون: David H. Adams, Evaggelia Liaskou, Margaret Corrigan, Sarah Akiror, Paul Woodward, Gwilym J. Webb, Gideon M. Hirschfield, Kathryn Arndtz, Christopher J. Weston, Yung-Yi Chen
المصدر: JHEP Reports, Vol 1, Iss 5, Pp 369-376 (2019)
JHEP Reports
بيانات النشر: Elsevier, 2019.
سنة النشر: 2019
مصطلحات موضوعية: Pathology, medicine.medical_specialty, medicine.medical_treatment, CD14, macrophage, Liver transplantation, Chronic liver disease, TGR-5 (G protein-coupled bile acid receptor 1, Primary sclerosing cholangitis, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal Medicine, Immunology and Allergy, Medicine, lcsh:RC799-869, 030304 developmental biology, 0303 health sciences, Hepatology, business.industry, CD68, GPBAR1/TGR-5), Monocyte, Gastroenterology, medicine.disease, Primary sclerosing cholangitis (PSC), 3. Good health, medicine.anatomical_structure, 030211 gastroenterology & hepatology, lcsh:Diseases of the digestive system. Gastroenterology, Steatohepatitis, business, Research Article
الوصف: Background & Aims Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammatory and fibrotic injury to the biliary tree. We sought to further delineate the contribution of macrophage lineages in PSC pathobiology. Methods Human liver tissues and/or blood samples from patients with PSC, primary biliary cholangitis, other non-cholestatic/non-autoimmune diseases, including alcohol-related liver disease and non-alcoholic steatohepatitis, as well as normal liver, were sourced from our liver transplantation program. Liver fibrosis was studied using Van Gieson staining, while the frequencies of infiltrating monocyte and macrophage lineages, both in the circulation and the liver, were investigated by flow cytometry, including the expression of TGR-5, a G protein-coupled receptor (GPBAR1/TGR-5). Results Significantly higher frequencies of CD68+CD206+ macrophages were detected in the livers of patients with PSC (median 19.17%; IQR 7.25–32.8%; n = 15) compared to those of patients with other liver diseases (median 12.05%; IQR 5.61–16.03%; n = 12; p = 0.0373). CD16+ monocytes, including both intermediate (CD14+CD16++) and non-classical (CD14dimCD16++) monocytes, were preferentially recruited into chronically diseased livers, with the highest recruitment ratios in PSC (median 15.83%; IQR 9.66–29.5%; n = 15), compared to other liver diseases (median 6.66%; IQR 2.88–11.64%, n = 14, p = 0.0152). The expression of TGR-5 on CD68+ intrahepatic macrophages was increased in chronic liver disease; TGR-5 expression on intrahepatic macrophages was highest in PSC (median 36.32%; IQR 17.71–63.61%; n = 6) and most TGR-5+ macrophages were CD68+CD206+ macrophages. Conclusions Underlying a potential role for macrophages in PSC pathobiology, we demonstrate, using patient-derived tissue, increased CD16+ monocyte recruitment and a higher frequency of CD68+CD206+ macrophages in the livers of patients with PSC; the CD68+CD206+ macrophage subset was associated with significantly higher TGR-5 expression in PSC. Lay summary Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease associated with progressive inflammation of the bile duct, leading to fibrosis and end-stage liver disease. In this study we explore the role of a type of immune cell, the macrophage, in contributing to PSC as a disease, hoping that our findings direct scientists towards new treatment targets. Our findings based on human liver and blood analyses demonstrate a greater frequency of a particular subset of immune cell, the CD68+CD206+ macrophage, with significantly higher TGR-5 expression on this subset in PSC.
Graphical Abstract Unlabelled Image
Highlights • CD68+CD206+ macrophage populations predominate in the liver tissue of patients with primary sclerosing cholangitis. • Intrahepatic CD16+ monocytes preferentially accumulate in the livers of patients with primary sclerosing cholangitis. • The expression of TGR-5 is increased in chronic liver disease. • TGR-5 expression on CD68+CD206+ intrahepatic macrophages is higher in patients with primary sclerosing cholangitis.
اللغة: English
تدمد: 2589-5559
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a3005a1170d8879cf0ff2d35bd1eafbTest
http://www.sciencedirect.com/science/article/pii/S2589555919301259Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....4a3005a1170d8879cf0ff2d35bd1eafb
قاعدة البيانات: OpenAIRE