Impaired Kupffer Cell Self-Renewal Alters the Liver Response to Lipid Overload during Non-alcoholic Steatohepatitis.
Immunity
; 53(3): 627-640.e5, 2020 09 15.
Article
in En
| MEDLINE
| ID: mdl-32562600
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lipid Metabolism
/
Non-alcoholic Fatty Liver Disease
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Cell Self Renewal
/
Kupffer Cells
/
Liver
Limits:
Animals
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2020
Type:
Article
Affiliation country:
France