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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / immunology*
  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / metabolism
  • Humans
  • Immunity, Innate
  • Inflammation Mediators / metabolism
  • Insulin Resistance / immunology*
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Lymphocytes / immunology*
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Obesity / immunology*
  • STAT4 Transcription Factor / genetics
  • STAT4 Transcription Factor / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*


  • Basic-Leucine Zipper Transcription Factors
  • Cytokines
  • Eomes protein, mouse
  • Inflammation Mediators
  • Nfil3 protein, mouse
  • STAT4 Transcription Factor
  • Stat4 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interleukin-12
  • Interferon-gamma