Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner

被引：861

作者：

Jaitin, Diego Adhemar ^{[1
]}

Adlung, Lorenz ^{[1
]}

Thaiss, Christoph A. ^{[1
,2
,3
,4
]}

Weiner, Assaf ^{[1
]}

Li, Baoguo ^{[1
]}

Descamps, Helene ^{[2
,3
,4
]}

Lundgren, Patrick ^{[2
,3
,4
]}

Bleriot, Camille ^{[5
]}

Liu, Zhaoyuan ^{[6
]}

Deczkowska, Aleksandra ^{[1
]}

Keren-Shaul, Hadas ^{[1
]}

David, Eyal ^{[1
]}

Zmora, Niv ^{[1
]}

Eldar, Shai Meron ^{[7
,8
]}

Lubezky, Nir ^{[7
,8
]}

Shibolet, Oren ^{[9
]}

Hill, David A. ^{[4
,10
]}

Lazar, Mitchell A. ^{[4
,11
]}

Colonna, Marco ^{[12
]}

Ginhoux, Florent ^{[5
,6
]}

Shapiro, Hagit ^{[1
]}

Elinav, Eran ^{[1
]}

Amit, Ido ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, IL-7610001 Rehovot, Israel

[2] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[3] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA

[4] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA

[5] ASTAR, Singapore Immunol Network SIgN, Biopolis, Singapore 138648, Singapore

[6] Shanghai Jiao Tong Univ, Shanghai Inst Immunol, Sch Med, Shanghai 200025, Peoples R China

[7] Tel Aviv Univ, Tel Aviv Med Ctr, Div Surg, IL-6997801 Tel Aviv, Israel

[8] Tel Aviv Univ, Sackler Fac Med, IL-6997801 Tel Aviv, Israel

[9] Tel Aviv Sourasky Med Ctr, Res Ctr Digest Tract & Liver Dis, IL-6423906 Tel Aviv, Israel

[10] Childrens Hosp Philadelphia, Dept Pediat, Div Allergy & Immunol, Philadelphia, PA 19104 USA

[11] Univ Penn, Perelman Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA

[12] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA

来源：

CELL | 2019年 / 178卷 / 03期

基金：

欧洲研究理事会; 以色列科学基金会;

关键词：

ADIPOSE-TISSUE; T-CELLS; PPAR-GAMMA; OBESITY; INFLAMMATION; MICROGLIA; PHENOTYPE; FAT;

D O I：

10.1016/j.cell.2019.05.054

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Immune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2(+) lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hyper-cholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.

引用

页码：686 / +

页数：27

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