2024-03-11 カロリンスカ研究所(KI)
<関連情報>
- https://news.ki.se/the-liver-immune-system-eats-up-bad-cholesterol
- https://www.nature.com/articles/s44161-024-00448-6
クッパー細胞がアテローム性脂質異常症への肝反応を決定する Kupffer cells dictate hepatic responses to the atherogenic dyslipidemic insult
Giada Di Nunzio,Sanna Hellberg,Yuyang Zhang,Osman Ahmed,Jiawen Wang,Xueming Zhang,Hanna M. Björck,Veronika Chizh,Ruby Schipper,Hanna Aulin,Roy Francis,Linn Fagerberg,Anton Gisterå,Jari Metso,Valentina Manfé,Anders Franco-Cereceda,Per Eriksson,Matti Jauhiainen,Carolina E. Hagberg,Peder S. Olofsson & Stephen G. Malin
Nature Cardiovascular Research Published:11 March 2024
DOI:https://doi.org/10.1038/s44161-024-00448-6
Abstract
Apolipoprotein-B (APOB)-containing lipoproteins cause atherosclerosis. Whether the vasculature is the initially responding site or if atherogenic dyslipidemia affects other organs simultaneously is unknown. Here we show that the liver responds to a dyslipidemic insult based on inducible models of familial hypercholesterolemia and APOB tracing. An acute transition to atherogenic APOB lipoprotein levels resulted in uptake by Kupffer cells and rapid accumulation of triglycerides and cholesterol in the liver. Bulk and single-cell RNA sequencing revealed a Kupffer-cell-specific transcriptional program that was not activated by a high-fat diet alone or detected in standard liver function or pathological assays, even in the presence of fulminant atherosclerosis. Depletion of Kupffer cells altered the dynamic of plasma and liver lipid concentrations, indicating that these liver macrophages help restrain and buffer atherogenic lipoproteins while simultaneously secreting atherosclerosis-modulating factors into plasma. Our results place Kupffer cells as key sentinels in organizing systemic responses to lipoproteins at the initiation of atherosclerosis.
