Innate Lymphoid Cells in the Induction of Obesity

Cell Rep. 2019 Jul 2;28(1):202-217.e7. doi: 10.1016/j.celrep.2019.06.016.


Complex interactions between immune cells are an important component in the induction of obesity. Here, we show that Il2rg-/-Rag2-/- mice lacking all lymphocytes are resistant to diet-induced obesity. Transplantation of bone marrow cells from Rag2-/- mice, which lack only acquired immune cells, into Il2rg-/-Rag2-/- mice abolishes this resistance, indicating a role for innate lymphoid cells (ILCs) in this process. Mice lacking ILC2 or ILC3 cells, but not natural killer cells, are resistant to obesity. Adoptive transfer of naive ILC2s isolated from the small intestine (SI), but not ILC2s from white adipose tissue (WAT), restores the induction of diet-induced obesity in Il2rg-/-Rag2-/- mice. Analysis of transcriptional differences reveals that SI-ILC2s express higher levels of IL-2 than do WAT-ILC2s and that blockade of IL-2 signaling impairs weight gain and reduces the populations of ILC2s and ILC3s in the SI, suggesting a role for the IL-2/ILC2/3 axis in the induction of obesity.

Keywords: ILC2; ILC3; common gamma chain; high-fat diet; innate lymphoid cells; interleukin-2; obesity; small intestine; white adipose tissue; γ(c).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / cytology*
  • Adipose Tissue, White / metabolism
  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Diet, High-Fat
  • Gastrointestinal Microbiome / genetics
  • Immunity, Innate
  • Interleukin Receptor Common gamma Subunit / genetics
  • Interleukin Receptor Common gamma Subunit / metabolism
  • Interleukin-2 / metabolism*
  • Intestine, Small / cytology*
  • Intestine, Small / metabolism
  • Killer Cells, Natural / immunology
  • Lymphocytes / cytology*
  • Lymphocytes / metabolism*
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / immunology*


  • DNA-Binding Proteins
  • Il2rg protein, mouse
  • Interleukin Receptor Common gamma Subunit
  • Interleukin-2
  • Rag2 protein, mouse