Volume 46, Issue 2, 21 February 2017, Pages 273–286


Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity

  • 1 Brigham and Women’s Hospital, Boston, MA 02115, USA
  • 2 Harvard Medical School, Boston, MA 02115, USA
  • 3 Education Research Centre, St. Vincent’s University Hospital, Dublin 4, Ireland
  • 4 School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland


AT1-ILCs are enriched in mouse and human adipose tissue and are predominantly tissue resident

AT1-ILCs kill adipose tissue macrophages (ATMs) and maintain ATM homeostasis

Subsets of AT1-ILCs infiltrate adipose tissue during the onset of obesity

In obesity, AT1-ILCs are reduced and lose their ability to kill


Adipose tissue has a dynamic immune system that adapts to changes in diet and maintains homeostatic tissue remodeling. Adipose type 1 innate lymphoid cells (AT1-ILCs) promote pro-inflammatory macrophages in obesity, but little is known about their functions at steady state. Here we found that human and murine adipose tissue harbor heterogeneous populations of AT1-ILCs. Experiments using parabiotic mice fed a high-fat diet (HFD) showed differential trafficking of AT1-ILCs, particularly in response to short- and long-term HFD and diet restriction. At steady state, AT1-ILCs displayed cytotoxic activity toward adipose tissue macrophages (ATMs). Depletion of AT1-ILCs and perforin deficiency resulted in alterations in the ratio of inflammatory to anti-inflammatory ATMs, and adoptive transfer of AT1-ILCs exacerbated metabolic disorder. Diet-induced obesity impaired AT1-ILC killing ability. Our findings reveal a role for AT1-ILCs in regulating ATM homeostasis through cytotoxicity and suggest that this function is relevant in both homeostasis and metabolic disease.


  • NK cells;
  • adipose tissue;
  • macrophages;
  • obesity;
  • cytotoxicity;
  • metabolism