Hepatic Stellate Cell-Immune Interactions in NASH DOI Creative Commons
James K. Carter, Scott L. Friedman

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: June 9, 2022

Nonalcoholic fatty liver disease (NAFLD) is the dominant cause of worldwide. steatohepatitis (NASH), a more aggressive presentation NAFLD, characterized by severe hepatocellular injury, inflammation, and fibrosis. Chronic inflammation heightened immune cell activity have emerged as hallmark features NASH key drivers fibrosis through activation hepatic stellate cells (HSCs). Recent advances in our understanding molecular cellular pathways highlighted extensive crosstalk between HSCs populations that strongly influences activity. Here, we review these findings, emphasizing roles immunity cell-cell interactions, exciting areas for future investigation.

Language: Английский

Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits DOI Creative Commons
Moritz Peiseler, Robert F. Schwabe, Jochen Hampe

et al.

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(4), P. 1136 - 1160

Published: June 22, 2022

Language: Английский

Citations

312
The biology of TREM receptors DOI Open Access
Marco Colonna

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(9), P. 580 - 594

Published: Feb. 7, 2023

Language: Английский

Citations

187
Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation DOI
Thomas Fabre, Alex Barron, Stephen M. Christensen

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(82)

Published: April 7, 2023

Macrophages are central orchestrators of the tissue response to injury, with distinct macrophage activation states playing key roles in fibrosis progression and resolution. Identifying populations found human fibrotic tissues could lead new treatments for fibrosis. Here, we used liver lung single-cell RNA sequencing datasets identify a subset CD9+TREM2+ macrophages that express SPP1, GPNMB, FABP5, CD63. In both murine hepatic pulmonary fibrosis, these were enriched at outside edges scarring adjacent activated mesenchymal cells. Neutrophils expressing MMP9, which participates TGF-β1, type 3 cytokines GM-CSF IL-17A coclustered macrophages. vitro, GM-CSF, IL-17A, TGF-β1 drive differentiation monocytes into scar-associated markers. Such differentiated cells degrade collagen IV but not I promote TGF-β1-induced deposition by models blocking or reduced expansion Our work identifies highly specific population assign profibrotic role across species tissues. It further provides strategy unbiased discovery, triage, preclinical validation therapeutic targets based on this fibrogenic population.

Language: Английский

Citations

152
Soluble TREM2 levels reflect the recruitment and expansion of TREM2+ macrophages that localize to fibrotic areas and limit NASH DOI Creative Commons
Tim Hendrikx, Florentina Porsch, Máté G. Kiss

et al.

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(5), P. 1373 - 1385

Published: June 21, 2022

Language: Английский

Citations

125
Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development DOI Creative Commons
Xiaochen Wang,

Qifeng He,

Chuanli Zhou

et al.

Immunity, Journal Year: 2022, Volume and Issue: 56(1), P. 58 - 77.e11

Published: Dec. 14, 2022

Language: Английский

Citations

118
TREM2 in the pathogenesis of AD: a lipid metabolism regulator and potential metabolic therapeutic target DOI Creative Commons

Li Ruiyang,

Qi Qin,

Han-Chen Yang

et al.

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: June 3, 2022

Triggering receptor expressed on myeloid cells 2 (TREM2) is a single-pass transmembrane immune that mainly microglia in the brain and macrophages periphery. Recent studies have identified TREM2 as risk factor for Alzheimer's disease (AD). Increasing evidence has shown can affect lipid metabolism both central nervous system (CNS) In CNS, affects of cholesterol, myelin, phospholipids promotes transition into disease-associated phenotype. periphery, influences by regulating onset progression obesity its complications, such hypercholesterolemia, atherosclerosis, nonalcoholic fatty liver disease. All these altered processes could influence pathogenesis AD through several means, including affecting inflammation, insulin resistance, pathologies. Herein, we will discuss potential pathway mediates to CNS Moreover, possibility may be key links peripheral under conditions, AD. This link due impacts integrity blood-brain barrier, introduce pathways which barrier. role lipids TREM2-associated treatments We propose some therapies targeting prospect limitations therapies.

Language: Английский

Citations

114
TREM2 dependent and independent functions of microglia in Alzheimer’s disease DOI Creative Commons
Jinchao Hou, Yun Chen,

Gary E. Grajales‐Reyes

et al.

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Dec. 23, 2022

Abstract Microglia are central players in brain innate immunity and have been the subject of extensive research Alzheimer’s disease (AD). In this review, we aim to summarize genetic functional discoveries that advanced our understanding microglia reactivity AD pathology. Given heightened risk posed by rare variants microglial triggering receptor expressed on myeloid cells 2 (TREM2), will focus studies addressing impact responses amyloid plaques, tauopathy demyelination pathologies mouse human. Finally, discuss implications recent TREM2 biology potential therapeutic strategies for AD.

Language: Английский

Citations

94
Nonalcoholic Fatty Liver Disease and the Gut-Liver Axis: Exploring an Undernutrition Perspective DOI Creative Commons
Kylynda C. Bauer, Paula Littlejohn, Victòria Ayala

et al.

Gastroenterology, Journal Year: 2022, Volume and Issue: 162(7), P. 1858 - 1875.e2

Published: March 3, 2022

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition affecting one quarter of the global population. Although primarily linked to obesity and metabolic syndrome, undernutrition altered (dysbiotic) gut microbiome influence NAFLD progression. Both prevalence are predicted considerably increase, but how undernourished contributes hepatic pathophysiology remains far less studied. Here, we present conditions with features, including kwashiorkor micronutrient deficiency. We then review microbiota-liver axis, highlighting key pathways progression within both overnutrition undernutrition. To conclude, identify challenges collaborative possibilities emerging multiomic research addressing pathology treatment NAFLD.

Language: Английский

Citations

86
Macrophage-derived Osteopontin (SPP1) Protects From Nonalcoholic Steatohepatitis DOI Creative Commons
Hui Han, Xiaodong Ge, Sai Santosh Babu Komakula

et al.

Gastroenterology, Journal Year: 2023, Volume and Issue: 165(1), P. 201 - 217

Published: April 5, 2023

Background & AimsNonalcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, hepatocyte ballooning degeneration, and fibrosis, all of which increase the risk progression to end-stage liver disease. Osteopontin (OPN, SPP1) plays an important role in macrophage (MF) biology, but whether MF-derived OPN affects NASH unknown.MethodsWe analyzed publicly available transcriptomic datasets from patients with NASH, used mice conditional overexpression or ablation Spp1 myeloid cells MFs, fed them a high-fat, fructose, cholesterol diet mimicking Western diet, induce NASH.ResultsThis study demonstrated that MFs high expression SPP1 are enriched nonalcoholic fatty disease (NAFLD), show metabolic not pro-inflammatory properties. Conditional knockin (Spp1KI Mye) hepatic macrophages LvMF) conferred protection, whereas knockout (Spp1ΔMye) worsened NASH. The protective effect was mediated induction arginase-2 (ARG2), enhanced acid oxidation (FAO) hepatocytes. Induction ARG2 stemmed production oncostatin-M (OSM) Spp1KI Mye mice. OSM activated STAT3 signaling, upregulated ARG2. In addition effects, also protected through sex-specific extrahepatic mechanisms.ConclusionMF-derived protects upregulating OSM, increases signaling. Further, ARG2-mediated FAO reduces steatosis. Therefore, enhancing OPN–OSM–ARG2 crosstalk between hepatocytes may be beneficial for Nonalcoholic unknown. We This mechanisms.

Language: Английский

Citations

74
Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation DOI
Satoru Sugimoto, Hebe Agustina Mena, Brian E. Sansbury

et al.

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(6), P. 775 - 790

Published: June 27, 2022

Language: Английский

Citations

73