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

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.

journal_name

Immunity

journal_title

Immunity

authors

Tran S,Baba I,Poupel L,Dussaud S,Moreau M,Gélineau A,Marcelin G,Magréau-Davy E,Ouhachi M,Lesnik P,Boissonnas A,Le Goff W,Clausen BE,Yvan-Charvet L,Sennlaub F,Huby T,Gautier EL

doi

10.1016/j.immuni.2020.06.003

subject

Has Abstract

pub_date

2020-09-15 00:00:00

pages

627-640.e5

issue

3

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(20)30233-8

journal_volume

53

pub_type

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