Your browser doesn't support javascript.
loading
Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development.
Wang, Xiaochen; He, Qifeng; Zhou, Chuanli; Xu, Yueyuan; Liu, Danhui; Fujiwara, Naoto; Kubota, Naoto; Click, Arielle; Henderson, Polly; Vancil, Janiece; Marquez, Cesia Ammi; Gunasekaran, Ganesh; Schwartz, Myron E; Tabrizian, Parissa; Sarpel, Umut; Fiel, Maria Isabel; Diao, Yarui; Sun, Beicheng; Hoshida, Yujin; Liang, Shuang; Zhong, Zhenyu.
Afiliación
  • Wang X; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • He Q; Department of General Surgery, Nanjing First Hospital, The Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing 210006, Jiangsu, China.
  • Zhou C; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Xu Y; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Duke Regeneration Center, Center for Advanced Genomic Technologies, Duke University Medical Center, Durham, NC 27710, USA.
  • Liu D; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Fujiwara N; Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Kubota N; Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Click A; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Henderson P; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Vancil J; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Marquez CA; Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Gunasekaran G; Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Schwartz ME; Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Tabrizian P; Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Sarpel U; Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Fiel MI; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Diao Y; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Duke Regeneration Center, Center for Advanced Genomic Technologies, Duke University Medical Center, Durham, NC 27710, USA.
  • Sun B; Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, China.
  • Hoshida Y; Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Liang S; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: shuang.liang@utsouthwestern.edu.
  • Zhong Z; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: zhenyu.zhong@utsouthwestern.edu.
Immunity ; 56(1): 58-77.e11, 2023 01 10.
Article en En | MEDLINE | ID: mdl-36521495
Obesity-induced chronic liver inflammation is a hallmark of nonalcoholic steatohepatitis (NASH)-an aggressive form of nonalcoholic fatty liver disease. However, it remains unclear how such a low-grade, yet persistent, inflammation is sustained in the liver. Here, we show that the macrophage phagocytic receptor TREM2, induced by hepatocyte-derived sphingosine-1-phosphate, was required for efferocytosis of lipid-laden apoptotic hepatocytes and thereby maintained liver immune homeostasis. However, prolonged hypernutrition led to the production of proinflammatory cytokines TNF and IL-1ß in the liver to induce TREM2 shedding through ADAM17-dependent proteolytic cleavage. Loss of TREM2 resulted in aberrant accumulation of dying hepatocytes, thereby further augmenting proinflammatory cytokine production. This ultimately precipitated a vicious cycle that licensed chronic inflammation to drive simple steatosis transition to NASH. Therefore, impaired macrophage efferocytosis is a previously unrecognized key pathogenic event that enables chronic liver inflammation in obesity. Blocking TREM2 cleavage to restore efferocytosis may represent an effective strategy to treat NASH.
Asunto(s)
Palabras clave

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Hipernutrición / Enfermedad del Hígado Graso no Alcohólico Límite: Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Hipernutrición / Enfermedad del Hígado Graso no Alcohólico Límite: Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos