- 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. Barreby et al. identify a distinct subpopulation of human resident liver myeloid cells that expresses factors that act in a protective fashion against oxidative stress associated with NAFLD. AD - Karolinska Univ Hosp, Karolinska Inst, Ctr Infect Med CIM, Dept Med Huddinge, Stockholm, Sweden AD - Karolinska Inst, Dept Physiol & Pharmacol, Solna, Sweden AD - Karolinska Inst CLINTEC, Dept Clin Sci Intervent & Technol, Div Transplantat Surg, Huddinge, Sweden AD - Karolinska Inst, Dept Microbiol, Tumor & Cell Biol MTC, Stockholm, Sweden AD - UCL, Inst Immun & Transplantat, Div Infect & Immun, London, England AD - Karolinska Inst, Dept Med Biochem & Biophys, Div Mol Neurobiol, Stockholm, Sweden AD - Karolinska Inst, Dept Med, Div Gastroenterol, Stockholm, Sweden AD - Friedrich Alexander Univ Erlangen Nurnberg, Dept Microbiome Res, Erlangen, Germany AD - Univ Freiburg, Fac Med, Med Ctr, Dept Med 2, Freiburg, Germany AD - Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Surg, Stockholm, Sweden AD - Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany AD - Univ Tubingen, Tubingen, Germany AD - AstraZeneca, BioPharmaceut R&D, Clin Pharmacol & Safety Sci, Translat Hepat Safety, Gothenburg, Sweden AD - Karolinska Univ Hosp, Karolinska Inst, Dept Med Huddinge, Cardio Metab Unit, Stockholm, Sweden AD - Karolinska Inst, Dept Lab Med, Div Clin Chem, Stockholm, Sweden
Human resident liver myeloid cells protect against metabolic stress in obesity
Morgantini C;
2023-01-01
Abstract
- 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. Barreby et al. identify a distinct subpopulation of human resident liver myeloid cells that expresses factors that act in a protective fashion against oxidative stress associated with NAFLD. AD - Karolinska Univ Hosp, Karolinska Inst, Ctr Infect Med CIM, Dept Med Huddinge, Stockholm, Sweden AD - Karolinska Inst, Dept Physiol & Pharmacol, Solna, Sweden AD - Karolinska Inst CLINTEC, Dept Clin Sci Intervent & Technol, Div Transplantat Surg, Huddinge, Sweden AD - Karolinska Inst, Dept Microbiol, Tumor & Cell Biol MTC, Stockholm, Sweden AD - UCL, Inst Immun & Transplantat, Div Infect & Immun, London, England AD - Karolinska Inst, Dept Med Biochem & Biophys, Div Mol Neurobiol, Stockholm, Sweden AD - Karolinska Inst, Dept Med, Div Gastroenterol, Stockholm, Sweden AD - Friedrich Alexander Univ Erlangen Nurnberg, Dept Microbiome Res, Erlangen, Germany AD - Univ Freiburg, Fac Med, Med Ctr, Dept Med 2, Freiburg, Germany AD - Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Surg, Stockholm, Sweden AD - Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany AD - Univ Tubingen, Tubingen, Germany AD - AstraZeneca, BioPharmaceut R&D, Clin Pharmacol & Safety Sci, Translat Hepat Safety, Gothenburg, Sweden AD - Karolinska Univ Hosp, Karolinska Inst, Dept Med Huddinge, Cardio Metab Unit, Stockholm, Sweden AD - Karolinska Inst, Dept Lab Med, Div Clin Chem, Stockholm, SwedenI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
