Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches

Cell, Journal Year: 2022, Volume and Issue: 185(2), P. 379 - 396.e38

Published: Jan. 1, 2022

The liver is the largest solid organ in body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of healthy and obese human murine combining single-cell CITE-seq, single-nuclei sequencing, transcriptomics, proteomics. By integrating these multi-omic datasets, provide validated strategies to reliably discriminate localize all hepatic cells, including population lipid-associated macrophages (LAMs) at bile ducts. We then align this across seven species, revealing conserved program bona fide Kupffer cells LAMs. also uncover respective spatially resolved cellular niches microenvironmental circuits driving their unique transcriptomic identities. demonstrate that LAMs are induced by local lipid exposure, leading induction steatotic regions liver, while cell development crucially depends on cross-talk with stellate via evolutionarily ALK1-BMP9/10 axis.

Language: Английский

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Macrophages in health and disease

Cell, Journal Year: 2022, Volume and Issue: 185(23), P. 4259 - 4279

Published: Nov. 1, 2022

Language: Английский

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Tissue-specific macrophages: how they develop and choreograph tissue biology

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(9), P. 563 - 579

Published: March 15, 2023

Macrophages are innate immune cells that form a 3D network in all our tissues, where they phagocytose dying and cell debris, complexes, bacteria other waste products. Simultaneously, produce growth factors signalling molecules — such activities not only promote host protection response to invading microorganisms but also crucial for organ development homeostasis. There is mounting evidence of macrophages orchestrating fundamental physiological processes, as blood vessel formation, adipogenesis, metabolism central peripheral neuronal function. In parallel, novel methodologies have led the characterization tissue-specific macrophages, with distinct subpopulations these showing different developmental trajectories, transcriptional programmes life cycles. Here, we summarize growing knowledge macrophage diversity how subsets orchestrate tissue We further interrelate ontogeny their core functions across is, events within niche may control functionality during development, homeostasis ageing. Finally, highlight open questions will need be addressed by future studies better understand subsets. important immunity infections clearing products from maintain health regulating metabolism, many biological processes. Elvira Mass co-workers discuss populations found throughout body, highlighting shared unique aspects functions.

Language: Английский

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Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits

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

Published: June 22, 2022

Language: Английский

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Hepatic inflammatory responses in liver fibrosis

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(10), P. 633 - 646

Published: July 3, 2023

Language: Английский

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Liver macrophages in health and disease

Immunity, Journal Year: 2022, Volume and Issue: 55(9), P. 1515 - 1529

Published: Sept. 1, 2022

Language: Английский

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Macrophage functional diversity in NAFLD — more than inflammation

Nature Reviews Endocrinology, Journal Year: 2022, Volume and Issue: 18(8), P. 461 - 472

Published: May 9, 2022

Language: Английский

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An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 79(2), P. 552 - 566

Published: April 14, 2023

Language: Английский

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Roles of macrophages in tumor development: a spatiotemporal perspective

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(9), P. 983 - 992

Published: July 10, 2023

Abstract Macrophages are critical regulators of tissue homeostasis but also abundant in the tumor microenvironment (TME). In both primary tumors and metastases, such tumor-associated macrophages (TAMs) seem to support development. While we know that TAMs dominant immune cells TME, their vast heterogeneity associated functions only just being unraveled. this review, outline various known TAM populations found thus far delineate specialized roles with main stages cancer progression. We discuss how may prime premetastatic niche enable growth a metastasis then subsequent metastasis-associated can secondary growth. Finally, speculate on challenges remain be overcome research.

Language: Английский

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Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming

Immunity, Journal Year: 2021, Volume and Issue: 54(9), P. 2089 - 2100.e8

Published: Aug. 31, 2021

Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive recognizing hepatocellular driven into state immune dysfunction, identify subset (referred as KC2) that cross-presents upon interleukin-2 (IL-2) administration, thus improving antiviral function cells. Removing MHC-I from all KCs, including KC2, selectively depleting KC2 impaired capacity IL-2 revert cell dysfunction induced by intrahepatic priming. In summary, sensing cross-presenting antigens, overcome tolerogenic potential hepatic microenvironment, suggesting new strategies boosting immunity.

Language: Английский

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