Single-cell RNA-Seq reveals changes in immune landscape in post-traumatic osteoarthritis DOI Creative Commons
Aimy Sebastian, Nicholas R. Hum, Jillian L. McCool

et al.

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

Published: July 29, 2022

Osteoarthritis (OA) is the most common joint disease, affecting over 300 million people world-wide. Accumulating evidence attests to important roles of immune system in OA pathogenesis. Understanding role various cells degeneration or repair after injury vital for improving therapeutic strategies treating OA. Post-traumatic osteoarthritis (PTOA) develops ~50% individuals who have experienced an articular trauma like anterior cruciate ligament (ACL) rupture. Here, using high resolution single-cell RNA sequencing, we delineated temporal dynamics cell accumulation mouse knee ACL Our study identified multiple types including neutrophils, monocytes, macrophages, B cells, T NK and dendritic cells. Monocytes macrophage populations showed dramatic changes injury. Further characterization monocytes macrophages reveled 9 major subtypes with unique transcriptomics signatures, a tissue resident Lyve1 hi Folr2 population Trem2 Fcrls + recruited both showing enrichment phagocytic genes growth factors such as Igf1 , Pdgfa Pdgfc. We also several induced repressed type-specific manner. This provides new insight into PTOA-associated microenvironment highlights that may play

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

313
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

196
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

154
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

128
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

115
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

76
Liver fibrosis in NAFLD/NASH: from pathophysiology towards diagnostic and therapeutic strategies DOI Creative Commons
Maurizio Parola, Massimo Pinzani

Molecular Aspects of Medicine, Journal Year: 2023, Volume and Issue: 95, P. 101231 - 101231

Published: Dec. 5, 2023

Liver fibrosis, as an excess deposition of extracellular matrix (ECM) components, results from chronic liver injury well persistent activation inflammatory response and fibrogenesis. fibrosis is a major determinant for disease (CLD) progression in the last two decades our understanding on molecular cellular mechanisms underlying fibrogenic CLD has dramatically improved, boosting pre-clinical studies clinical trials designed to find novel therapeutic approaches. From these several critical concepts have emerged, starting reveal complexity pro-fibrotic microenvironment which involves very complex, dynamic interrelated interactions between different hepatic extrahepatic cell populations. This review will offer first recapitulation established pathophysiological basic principles by intentionally focus attention NAFLD/NASH, metabolic-related form with high impact general population emerging leading cause worldwide. NAFLD/NASH-related pro-inflammatory profibrogenic be analysed information cells, mediators signalling pathways taken advantage methodological approaches techniques (single genomics, imaging mass cytometry, vitro two- three-dimensional models, etc.). We next overview recent advancement diagnostic prognostic tools, including serum biomarkers polygenic scores, support analysis biopsies. Finally, this provide current therapies treatment NAFLD/NASH patients.

Language: Английский

Citations

74