Hepatic leukocyte immunoglobulin-like receptor B4 (LILRB4) attenuates nonalcoholic fatty liver disease via SHP1-TRAF6 pathway

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Yao LuJingjing Cai

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent liver pathology characterized by hepatic steatosis and commonly accompanied by systematic inflammation and metabolic disorder. Despite an accumulating number of studies, no pharmacological strategy is available to treat this condition in the clinic. In this study, we applied extensive gain- and loss-of-function approaches to identify the key immune factor leukocyte immunoglobulin-like receptor B4 (LILRB4) as a negative regulator of NAFLD. The hepatocyte-specific knockout of LILRB4 (LILRB4-HKO) exacerbated high-fat diet-induced insulin resistance, glucose metabolic imbalance, hepatic lipid accumulation, and systematic inflammation in mice, whereas LILRB4 overexpression in hepatocytes showed a completely opposite phenotype relative to that of LILRB4-HKO mice when compared with their corresponding controls. Further investigations of molecular mechanisms demonstrated that LILRB4 recruits SHP1 to inhibit TRAF6 ubiquitination and subsequent inactivation of nuclear factor kappa B and mitogen-activated protein kinase cascades. From a therapeutic perspective, the overexpression of LILRB4 in a genetic model of NAFLD, ob/ob mice, largely reversed the inherent hepatic st...Continue Reading

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Citations

May 31, 2018·Medicinal Research Reviews·Jingjing CaiHongliang Li
Jan 16, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Dong Kwon Yang, Dong-Gyu Jo
Jan 18, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jingjing CaiHongliang Li
Jan 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Simone BrioschiMarco Colonna
Apr 14, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Heng ZhouQi-Zhu Tang
Sep 6, 2019·International Journal of Endocrinology·Fang WangZhaohui Mo
May 1, 2021·Antibody Therapeutics·Mi DengCheng Cheng Zhang
Jun 8, 2021·Frontiers in Pharmacology·Liuran LiYanzhen Cheng

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Methods Mentioned

BETA
ELISA
transgenic
immunoprecipitation
PCR
Protein Assay
electrophoresis
ubiquitination
transfection
deubiquitination

Software Mentioned

DP2
Image Lab
SPSS
BSW

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