TREM-2 plays a protective role in cholestasis by acting as a negative regulator of inflammation.
TREM receptors
cholangiopathies
inflammation
innate immunity
liver resident macrophages
ursodeoxycholic acid
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
03
08
2021
revised:
19
05
2022
accepted:
22
05
2022
pubmed:
25
6
2022
medline:
21
9
2022
entrez:
24
6
2022
Statut:
ppublish
Résumé
Inflammation, particularly that mediated by bacterial components translocating from the gut to the liver and binding to toll-like receptors (TLRs), is central to cholestatic liver injury. The triggering receptor expressed on myeloid cells-2 (TREM-2) inhibits TLR-mediated signaling and exerts a protective role in hepatocellular injury and carcinogenesis. This study aims to evaluate the role of TREM-2 in cholestasis. TREM-2 expression was analyzed in the livers of patients with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC), and in mouse models of cholestasis. Wild-type (WT) and Trem-2 deficient (Trem-2 TREM-2 expression was upregulated in the livers of patients with PBC or PSC, and in murine models of cholestasis. Compared to WT, the response to bile duct ligation (BDL)-induced obstructive cholestasis or alpha-naphtylisothiocyanate (ANIT)-induced cholestasis was exacerbated in Trem-2 TREM-2 acts as a negative regulator of inflammation during cholestasis, representing a novel potential therapeutic target. Cholestasis (the reduction or cessation of bile flow) causes liver injury. This injury is exacerbated when gut-derived bacterial components interact with receptors (specifically Toll-like receptors or TLRs) on liver-resident immune cells, promoting inflammation. Herein, we show that the anti-inflammatory receptor TREM-2 dampens TLR-mediated signaling and hence protects against cholestasis-induced liver injury. Thus, TREM-2 could be a potential therapeutic target in cholestasis.
Sections du résumé
BACKGROUND & AIMS
Inflammation, particularly that mediated by bacterial components translocating from the gut to the liver and binding to toll-like receptors (TLRs), is central to cholestatic liver injury. The triggering receptor expressed on myeloid cells-2 (TREM-2) inhibits TLR-mediated signaling and exerts a protective role in hepatocellular injury and carcinogenesis. This study aims to evaluate the role of TREM-2 in cholestasis.
METHODS
TREM-2 expression was analyzed in the livers of patients with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC), and in mouse models of cholestasis. Wild-type (WT) and Trem-2 deficient (Trem-2
RESULTS
TREM-2 expression was upregulated in the livers of patients with PBC or PSC, and in murine models of cholestasis. Compared to WT, the response to bile duct ligation (BDL)-induced obstructive cholestasis or alpha-naphtylisothiocyanate (ANIT)-induced cholestasis was exacerbated in Trem-2
CONCLUSIONS
TREM-2 acts as a negative regulator of inflammation during cholestasis, representing a novel potential therapeutic target.
LAY SUMMARY
Cholestasis (the reduction or cessation of bile flow) causes liver injury. This injury is exacerbated when gut-derived bacterial components interact with receptors (specifically Toll-like receptors or TLRs) on liver-resident immune cells, promoting inflammation. Herein, we show that the anti-inflammatory receptor TREM-2 dampens TLR-mediated signaling and hence protects against cholestasis-induced liver injury. Thus, TREM-2 could be a potential therapeutic target in cholestasis.
Identifiants
pubmed: 35750136
pii: S0168-8278(22)00372-5
doi: 10.1016/j.jhep.2022.05.044
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Anti-Inflammatory Agents
0
Interleukin-33
0
Lipopolysaccharides
0
Membrane Glycoproteins
0
Receptors, Immunologic
0
Trem2 protein, mouse
0
Triggering Receptor Expressed on Myeloid Cells-1
0
Ursodeoxycholic Acid
724L30Y2QR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
991-1004Subventions
Organisme : Medical Research Council
ID : MR/K001949/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K0019494/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R023026/1
Pays : United Kingdom
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.