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Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner.
Jaitin, Diego Adhemar; Adlung, Lorenz; Thaiss, Christoph A; Weiner, Assaf; Li, Baoguo; Descamps, Hélène; Lundgren, Patrick; Bleriot, Camille; Liu, Zhaoyuan; Deczkowska, Aleksandra; Keren-Shaul, Hadas; David, Eyal; Zmora, Niv; Eldar, Shai Meron; Lubezky, Nir; Shibolet, Oren; Hill, David A; Lazar, Mitchell A; Colonna, Marco; Ginhoux, Florent; Shapiro, Hagit; Elinav, Eran; Amit, Ido.
Afiliação
  • Jaitin DA; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Adlung L; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Thaiss CA; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 1910
  • Weiner A; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Li B; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Descamps H; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medici
  • Lundgren P; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medici
  • Bleriot C; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Biopolis, Singapore 138648, Singapore.
  • Liu Z; Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
  • Deczkowska A; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Keren-Shaul H; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • David E; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Zmora N; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Eldar SM; Division of Surgery, Tel-Aviv Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • Lubezky N; Division of Surgery, Tel-Aviv Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • Shibolet O; Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel.
  • Hill DA; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Allergy and Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Lazar MA; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Colonna M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Ginhoux F; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Biopolis, Singapore 138648, Singapore; Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
  • Shapiro H; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Elinav E; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: eran.elinav@weizmann.ac.il.
  • Amit I; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: ido.amit@weizmann.ac.il.
Cell ; 178(3): 686-698.e14, 2019 07 25.
Article em En | MEDLINE | ID: mdl-31257031
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 hypercholesterolemia, 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glicoproteínas de Membrana / Receptores Imunológicos / Macrófagos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Israel

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glicoproteínas de Membrana / Receptores Imunológicos / Macrófagos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Israel