Stellate Cells, Hepatocytes, and Endothelial Cells Imprint the Kupffer Cell Identity on Monocytes Colonizing the Liver Macrophage Niche

被引：472

作者：

Bonnardel, Johnny ^{[1
,2
]}

T'Jonck, Wouter ^{[1
,2
]}

Gaublomme, Djoere ^{[3
,4
]}

Browaeys, Robin ^{[5
,6
]}

Scott, Charlotte L. ^{[1
,2
,7
]}

Martens, Liesbet ^{[2
,5
]}

Vanneste, Bavo ^{[1
,2
]}

De Prijck, Sofie ^{[1
,2
]}

Nedospasov, Sergei A. ^{[8
,9
]}

Kremer, Anna ^{[2
,10
]}

Van Hamme, Evelien ^{[2
,10
]}

Borghgraef, Peter ^{[2
,10
]}

Toussaint, Wendy ^{[4
,11
]}

De Bleser, Pieter ^{[2
,5
]}

Mannaerts, Inge ^{[12
]}

Beschin, Alain ^{[13
,14
]}

van Grunsven, Leo A. ^{[12
]}

Lambrecht, Bart N. ^{[4
,11
]}

Taghon, Tom ^{[15
]}

Lippens, Saskia ^{[2
,10
]}

Elewaut, Dirk ^{[3
,4
]}

Saeys, Yvan ^{[5
,6
]}

Guilliams, Martin ^{[1
,2
]}

机构：

[1] VIB Ctr Inflammat Res, Lab Myeloid Cell Ontogeny & Funct Specializat, Ghent, Belgium

[2] Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium

[3] VIB Ctr Inflammat Res, Unit Mol Immunol & Inflammat, Ghent, Belgium

[4] Univ Ghent, Dept Internal Med & Pediat, Ghent, Belgium

[5] VIB Ctr Inflammat Res, Data Min & Modeling Biomed, Ghent, Belgium

[6] Univ Ghent, Dept Appl Math Comp Sci & Stat, Ghent, Belgium

[7] Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland

[8] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, Russia

[9] Lomonosov Moscow State Univ, Fac Biol, Moscow, Russia

[10] VIB, VIB Bioimaging Core, Ghent, Belgium

[11] VIB Ctr Inflammat Res, Lab Mucosal Immunol & Immunoregulat, Ghent, Belgium

[12] Vrije Univ Brussel, Liver Cell Biol Res Grp, Brussels, Belgium

[13] VIB Ctr Inflammat Res, Myeloid Cell Immunol Lab, Brussels, Belgium

[14] Vrije Univ Brussel, Lab Cellular & Mol Immunol, Brussels, Belgium

[15] Univ Ghent, Dept Diagnost Sci, Ghent, Belgium

来源：

IMMUNITY | 2019年 / 51卷 / 04期

关键词：

GENE-EXPRESSION; TISSUE; SIGNALS; LIGHT;

D O I：

10.1016/j.immuni.2019.08.017

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Macrophages are strongly adapted to their tissue of residence. Yet, little is known about the cell-cell interactions that imprint the tissue-specific identities of macrophages in their respective niches. Using conditional depletion of liver Kupffer cells, we traced the developmental stages of monocytes differentiating into Kupffer cells and mapped the cellular interactions imprinting the Kupffer cell identity. Kupffer cell loss induced tumor necrosis factor (TNF)- and interleukin-1 (IL-1) receptor-dependent activation of stellate cells and endothelial cells, resulting in the transient production of chemokines and adhesion molecules orchestrating monocyte engraftment. Engrafted circulating monocytes transmigrated into the perisinusoidal space and acquired the liver-associated transcription factors inhibitor of DNA 3 (ID3) and liver X receptor-alpha (LXR-alpha). Coordinated interactions with hepatocytes induced ID3 expression, whereas endothelial cells and stellate cells induced LXR-alpha via a synergistic NOTCH-BMP pathway. This study shows that the Kupffer cell niche is composed of stellate cells, hepatocytes, and endothelial cells that together imprint the liver-specific macrophage identity.

引用

页码：638 / 654

页数：17

共 42 条

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