Human resident liver myeloid cells protect against metabolic stress in obesity.

Autor: Barreby E; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Strunz B; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Nock S; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Naudet L; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Shen JX; Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden., Johansson H; Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet (CLINTEC), Huddinge, Sweden., Sönnerborg I; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.; Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet (CLINTEC), Huddinge, Sweden., Ma J; Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden., Urgard E; Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden., Pallett LJ; Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London, United Kingdom., Hu Y; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Fardellas A; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Azzimato V; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.; BioPharmaceuticals R&D, Clinical Pharmacology and Safety Sciences, Translational Hepatic Safety, AstraZeneca, Gothenburg, Sweden., Vankova A; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Levi L; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Morgantini C; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.; Cardio Metabolic Unit, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Maini MK; Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London, United Kingdom., Stål P; Division of Gastroenterology, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden., Rosshart SP; Department of Microbiome Research, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.; Department of Medicine II, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany., Coquet JM; Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden., Nowak G; Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet (CLINTEC), Huddinge, Sweden., Näslund E; Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden., Lauschke VM; Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.; Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.; University of Tuebingen, Tuebingen, Germany., Ellis E; Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet (CLINTEC), Huddinge, Sweden., Björkström NK; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Chen P; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. ping.chen@ki.se.; Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. ping.chen@ki.se., Aouadi M; Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. myriam.aouadi@ki.se.
Jazyk: angličtina
Zdroj: Nature metabolism [Nat Metab] 2023 Jul; Vol. 5 (7), pp. 1188-1203. Date of Electronic Publication: 2023 Jul 06.
DOI: 10.1038/s42255-023-00834-7
Abstrakt: Although multiple populations of macrophages have been described in the human liver, their function and turnover in patients with obesity at high risk of developing non-alcoholic fatty liver disease (NAFLD) and cirrhosis are currently unknown. Herein, we identify a specific human population of resident liver myeloid cells that protects against the metabolic impairment associated with obesity. By studying the turnover of liver myeloid cells in individuals undergoing liver transplantation, we find that liver myeloid cell turnover differs between humans and mice. Using single-cell techniques and flow cytometry, we determine that the proportion of the protective resident liver myeloid cells, denoted liver myeloid cells 2 (LM2), decreases during obesity. Functional validation approaches using human 2D and 3D cultures reveal that the presence of LM2 ameliorates the oxidative stress associated with obese conditions. Our study indicates that resident myeloid cells could be a therapeutic target to decrease the oxidative stress associated with NAFLD.
(© 2023. The Author(s).)
Databáze: MEDLINE
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