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Immunity. 2016 Aug 16;45(2):428-41. doi: 10.1016/j.immuni.2016.06.016. Epub 2016 Aug 2.

Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance.

Author information

1
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
2
Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
3
Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France.
4
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.

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.

PMID:
27496734
PMCID:
PMC5004886
DOI:
10.1016/j.immuni.2016.06.016
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no financial conflicts of interest.

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