Impaired Kupffer Cell Self-Renewal Alters the Liver Response to Lipid Overload during Non-alcoholic Steatohepatitis

6533b850fe1ef96bd12a861f

RESEARCH PRODUCT

Impaired Kupffer Cell Self-Renewal Alters the Liver Response to Lipid Overload during Non-alcoholic Steatohepatitis

Sébastien Dussaud Alexandre Boissonnas Björn E. Clausen Genevieve Marcelin Emmanuel L. Gautier Sophie Tran Melissa Ouhachi Lucie Poupel Ines Baba Philippe Lesnik Thierry Huby Elissa Magréau-davy Florian Sennlaub Laurent Yvan-charvet Wilfried Le Goff Adélaïde Gélineau Martine Moreau

subject

0301 basic medicine [SDV]Life Sciences [q-bio]Ontogeny MESH: Cell Self Renewal Self renewal MESH: Monocytes MESH: Mice Knockout Mice 0302 clinical medicine Non-alcoholic Fatty Liver Disease Immunology and Allergy Kupffer cells MESH: Animals Cell Self Renewal MESH: Lipid Metabolism Mice Knockout Kupffer cell Lipids Research Highlight macrophages [SDV] Life Sciences [q-bio]Infectious Diseases medicine.anatomical_structure Liver 030220 oncology & carcinogenesis monocytes medicine.medical_specialty non-alcoholic steatohepatitis (NASH)Immunology Biology 03 medical and health sciences MESH: Mice Inbred C57BL MESH: Cell Proliferation Internal medicine medicine Animals Liver damage MESH: Mice Cell Proliferation MESH: Non-alcoholic Fatty Liver Disease Triglyceride storage Non alcoholic Lipid Metabolism medicine.disease MESH: Lipids eye diseases Mice Inbred C57BL MESH: Kupffer Cells 030104 developmental biology Endocrinology Steatohepatitis Homeostasis MESH: Liver

description

International audience; Kupffer cells (KCs) are liver-resident macrophages that self-renew by proliferation in the adult independently from monocytes. However, how they are maintained during non-alcoholic steatohepatitis (NASH) remains ill defined. We found that a fraction of KCs derived from Ly-6C+ monocytes during NASH, underlying impaired KC self-renewal. Monocyte-derived KCs (MoKCs) gradually seeded the KC pool as disease progressed in a response to embryo-derived KC (EmKC) death. Those MoKCs were partly immature and exhibited a pro-inflammatory status compared to EmKCs. Yet, they engrafted the KC pool for the long term as they remained following disease regression while acquiring mature EmKC markers. While KCs as a whole favored hepatic triglyceride storage during NASH, EmKCs promoted it more efficiently than MoKCs, and the latter exacerbated liver damage, highlighting functional differences among KCs with different origins. Overall, our data reveal that KC homeostasis is impaired during NASH, altering the liver response to lipids, as well as KC ontogeny.

year	journal	country	edition	language
2020-09-01	Immunity

https://doi.org/10.1016/j.immuni.2020.06.003