Kupffer cell-like syncytia replenish resident macrophage function in the fibrotic liver.

Peiseler, Moritz; Araujo David, Bruna; Zindel, Joel; Surewaard, Bas G J; Lee, Woo-Yong; Heymann, Felix; Nusse, Ysbrand; Castanheira, Fernanda V S; Shim, Raymond; Guillot, Adrien; Bruneau, Alix; Atif, Jawairia; Perciani, Catia; Ohland, Christina; Ganguli Mukherjee, Priyanka; Niehrs, Annika; Thuenauer, Roland; Altfeld, Marcus; Amrein, Mathias; Liu, Zhaoyuan; ... (2023). Kupffer cell-like syncytia replenish resident macrophage function in the fibrotic liver. Science, 381(6662), pp. 1-16. American Association for the Advancement of Science 10.1126/science.abq5202

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Kupffer cells (KCs) are localized in liver sinusoids but extend pseudopods to parenchymal cells to maintain their identity and serve as the body's central bacterial filter. Liver cirrhosis drastically alters vascular architecture, but how KCs adapt is unclear. We used a mouse model of liver fibrosis and human tissue to examine immune adaptation. Fibrosis forced KCs to lose contact with parenchymal cells, down-regulating "KC identity," which rendered them incapable of clearing bacteria. Commensals stimulated the recruitment of monocytes through CD44 to a spatially distinct vascular compartment. There, recruited monocytes formed large aggregates of multinucleated cells (syncytia) that expressed phenotypical KC markers and displayed enhanced bacterial capture ability. Syncytia formed via CD36 and were observed in human cirrhosis as a possible antimicrobial defense that evolved with fibrosis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery

UniBE Contributor:

Zindel, Joel

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1095-9203

Publisher:

American Association for the Advancement of Science

Language:

English

Submitter:

Pubmed Import

Date Deposited:

12 Sep 2023 12:29

Last Modified:

12 Sep 2023 12:38

Publisher DOI:

10.1126/science.abq5202

PubMed ID:

37676943

BORIS DOI:

10.48350/186142

URI:

https://boris.unibe.ch/id/eprint/186142

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