title: Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance.
abstract: Innate lymphoid cells (ILCs) function to protect epithelial barriers against pathogens and maintain tissue homeostasis in both barrier and non-barrier tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease. Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but phenotypically and functionally distinct from adipose mature natural killer (NK) and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s maintained long-term tissue residency. Diet-induced obesity drove early production of interleukin (IL)-12 in adipose tissue depots and led to the selective proliferation and accumulation of adipose-resident ILC1s in a manner dependent on the IL-12 receptor and STAT4. ILC1-derived interferon-γ was necessary and sufficient to drive proinflammatory macrophage polarization to promote obesity-associated insulin resistance. Thus, adipose-resident ILC1s contribute to obesity-related pathology in response to dysregulated local proinflammatory cytokine production.
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Timothy E
authors: TE
authors: O'Sullivan
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Moritz
authors: M
authors: Rapp
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Xiying
authors: X
authors: Fan
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Orr-El
authors: OE
authors: Weizman
authors: Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors: Priya
authors: P
authors: Bhardwaj
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Nicholas M
authors: NM
authors: Adams
authors: Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France.
authors: Thierry
authors: T
authors: Walzer
authors: Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors: Andrew J
authors: AJ
authors: Dannenberg
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: sunj@mskcc.org.
authors: Joseph C
authors: JC
authors: Sun
mesh_terms: D000273:Adipose Tissue / Q000276:immunology*; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000276:immunology*; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D016207:Cytokines; C491198:Eomes protein, mouse; D018836:Inflammation Mediators; C497441:Nfil3 protein, mouse; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D018664:Interleukin-12; D007371:Interferon-gamma