法国索邦大学Emmanuel L. Gautier研究小组发现，非酒精性脂肪性肝炎（NASH）期间库普弗细胞（KC）自我更新的受损改变了肝脏对脂质超负荷的反应。这一研究成果于2020年6月19日在线发表在《免疫》上。

Author: Sophie Tran, Ines Baba, Lucie Poupel, Sébastien Dussaud, Martine Moreau, Adélade Gélineau, Geneviève Marcelin, Elissa Magréau-Davy, Melissa Ouhachi, Philippe Lesnik, Alexandre Boissonnas, Wilfried Le Goff, Bjrn E. Clausen, Laurent Yvan-Charvet, Florian Sennlaub, Thierry Huby, Emmanuel L. Gautier

Issue&Volume: 2020-06-19

Abstract: Kupffer cells (KCs) are liver-resident macrophages that self-renew by proliferationin the adult independently from monocytes. However, how they are maintained duringnon-alcoholic steatohepatitis (NASH) remains ill defined. We found that a fractionof 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-derivedKC (EmKC) death. Those MoKCs were partly immature and exhibited a pro-inflammatorystatus compared to EmKCs. Yet, they engrafted the KC pool for the long term as theyremained following disease regression while acquiring mature EmKC markers. While KCsas a whole favored hepatic triglyceride storage during NASH, EmKCs promoted it moreefficiently than MoKCs, and the latter exacerbated liver damage, highlighting functionaldifferences among KCs with different origins. Overall, our data reveal that KC homeostasisis impaired during NASH, altering the liver response to lipids, as well as KC ontogeny.

DOI: 10.1016/j.immuni.2020.06.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30233-8