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

• DOI: 10.1126/science.abq5202
• Publication Date: 2023-09-07T17:58:56Z
• Authors: Moritz Peiseler; Bruna Araujo David; Joel Zindel; Bas G. J. Surewaard; Woo-Yong Lee; Felix Heymann; Ysbrand Nusse; Fernanda V. S. Ca...; Raymond Shim; Adrien Guillot; Alix Bruneau; Jawairia Atif; Catia Perciani; Christina Ohland; Priyanka Ganguli ...; Annika Niehrs; Roland Thuenauer; Marcus Altfeld; Mathias Amrein; Zhaoyuan Liu; Paul M. K. Gordon; Kathy McCoy; Justin Deniset; Sonya MacParland; Florent Ginhoux; Frank Tacke; Paul Kubes
• Keywords: Kupffer cell; Syncytium; Liver cytology

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