Nature Immunology, Journal Year: 2025, Volume and Issue: 26(1), P. 29 - 41
Published: Jan. 1, 2025
Language: Английский
Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(9), P. 580 - 594
Published: Feb. 7, 2023
Language: Английский
Citations
185
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
148
Immunity, Journal Year: 2022, Volume and Issue: 56(1), P. 58 - 77.e11
Published: Dec. 14, 2022
Language: Английский
Citations
116
Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(4), P. 572 - 578
Published: April 10, 2023
Abstract Non-alcoholic fatty liver disease (NAFLD) is a common, progressive strongly associated with the metabolic syndrome. It unclear how progression of NAFLD towards cirrhosis translates into systematic changes in circulating proteins. Here, we provide detailed proteo-transcriptomic map steatohepatitis and fibrosis during NAFLD. In this multicentre proteomic study, characterize 4,730 proteins 306 patients histologically characterized integrate transcriptomic analysis paired tissue. We identify signatures for active advanced fibrosis, correlate these hepatic transcriptomics to develop signature 31 markers. Deconvolution by single-cell RNA sequencing reveals cell types likely contribute progression. As an exemplar use as non-invasive diagnostic, logistic regression establishes composite model comprising four (ADAMTSL2, AKR1B10, CFHR4 TREM2), body mass index type 2 diabetes mellitus status, at-risk steatohepatitis.
Language: Английский
Citations
80
Nature Immunology, Journal Year: 2023, Volume and Issue: 24(9), P. 1423 - 1433
Published: July 20, 2023
Language: Английский
Citations
66
Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2023, Volume and Issue: 15(6), P. 1311 - 1324
Published: Jan. 1, 2023
Nonalcoholic fatty liver disease (NAFLD) is the manifestation of metabolic syndrome. NAFLD constitutes a spectrum pathologies ranging from simple hepatic steatosis (nonalcoholic liver) to more progressive form steatohepatitis and fibrosis, which can culminate in cirrhosis hepatocellular carcinoma. Macrophages play multiple roles context pathogenesis by regulating inflammatory responses homeostasis thereby may represent an attractive therapeutic target. Advances high-resolution methods have highlighted extraordinary heterogeneity plasticity macrophage populations activation states thereof. Harmful/disease-promoting as well beneficial/restorative phenotypes co-exist are dynamically regulated, thus this complexity must be taken into consideration strategies concerning targeting. Macrophage includes their distinct ontogeny (embryonic Kupffer cells vs bone marrow-/monocyte-derived macrophages) functional phenotype, for example, phagocytes, lipid- scar-associated macrophages, or restorative macrophages. Here, we discuss multifaceted role macrophages steatosis, steatohepatitis, transition fibrosis carcinoma, focusing on both beneficial maladaptive functions at different stages. We also highlight systemic aspect dysregulation illustrate contribution reciprocal crosstalk between organs compartments (eg, gut-liver axis, adipose tissue, cardiohepatic interactions). Furthermore, current state development pharmacologic treatment options targeting biology.
Language: Английский
Citations
46
Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(5)
Published: May 1, 2023
Language: Английский
Citations
45
Hepatology, Journal Year: 2024, Volume and Issue: unknown
Published: Feb. 13, 2024
Liver cancer is the third leading cause of cancer-related deaths and ranks as sixth most prevalent type globally. NAFLD or metabolic dysfunction-associated steatotic liver disease, its more severe manifestation, NASH steatohepatitis (MASH), pose a significant global health concern, affecting approximately 20%-25% population. The increased prevalence disease MASH parallel to increasing rates obesity-associated diseases, including 2 diabetes, insulin resistance, fatty diseases. can progress MASH-related HCC (MASH-HCC) in about 2% cases each year, influenced by various factors such genetic mutations, carcinogen exposure, immune microenvironment, microbiome. MASH-HCC exhibits distinct molecular characteristics compared other causes affects both men women equally. management early intermediate-stage typically involves surgery locoregional therapies, while advanced treated with systemic anti-angiogenic therapies checkpoint inhibitors. In this comprehensive review, we consolidate previous research findings also providing current insights into intricate processes underlying development. We delve MASH-HCC-associated variations somatic progression models, multiomics analysis, immunological microenvironmental impacts, discuss targeted/combined overcome evasion biomarkers recognize treatment responders. By furthering our comprehension mechanisms MASH-HCC, goal catalyze advancement potent strategies, ultimately enhanced patient outcomes.
Language: Английский
Citations
43
Nature Cardiovascular Research, Journal Year: 2024, Volume and Issue: 3(3), P. 269 - 282
Published: March 12, 2024
Abstract Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in intimal layer arteries, its main complications—myocardial infarction stroke—are leading cause mortality worldwide 1,2 . Recent studies have identified triggering receptor expressed on myeloid cells 2 (TREM2), lipid-sensing regulating cell functions 3 , to be highly macrophage foam experimental human atherosclerosis 4 However, role TREM2 not fully known. Here we show that hematopoietic or global deficiency increased, whereas agonism decreased, necrotic core formation early atherosclerosis. We demonstrate essential for efferocytosis capacities macrophages survival lipid-laden macrophages, indicating crucial maintaining balance between death clearance dead atherosclerotic lesions, thereby controlling plaque necrosis.
Language: Английский
Citations
29
Immunity, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Our understanding of the functional heterogeneity resident versus recruited macrophages in diseased liver is limited. A population lipid-associated (LAMs) has been reported to populate alongside Kupffer cells (KCs). However, precise roles these distinct macrophage subsets remain elusive. Here, using proteogenomics, we have identified LAMs multiple models injury. Moreover, found that this phenotype not specific macrophages, as a subset KCs can also adopt LAM-like mouse and human liver. By combining genetic targeting populations, determined both play crucial tissue repair. Specifically, triggering receptor expressed on myeloid 2 (TREM2) expression either or required for efficient clearance dying cells, enhancing repair preventing exacerbated fibrosis.
Language: Английский
Citations
3