Innate Lymphoid Cells in the Induction of Obesity

• Published in: Cell reports (Cambridge) Vol. 28; no. 1; pp. 202 - 217.e7
• Main Authors: Sasaki, Takaharu, Moro, Kazuyo, Kubota, Tetsuya, Kubota, Naoto, Kato, Tamotsu, Ohno, Hiroshi, Nakae, Susumu, Saito, Hirohisa, Koyasu, Shigeo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02-07-2019; Elsevier
• Subjects: common gamma chain; high-fat diet; ILC2; ILC3; innate lymphoid cells; interleukin-2; obesity; small intestine; white adipose tissue; ILC2; γc; ILC3; interleukin-2; white adipose tissue; high-fat diet; common gamma chain; small intestine; innate lymphoid cells; obesity; γ(c)
• ISSN: 2211-1247; 2211-1247
• 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.
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•Innate lymphoid cells are involved in the induction of diet-induced obesity•ILC2s and ILC3s but not ILC1/NK/exILC3 cells are involved in the induction of obesity•SI-ILC2s but not WAT-ILC2s are involved in the induction of obesity•IL-2 is critical for the maintenance and function of SI-ILC2s and ILC3s
Innate lymphoid cells (ILCs) are recently identified lymphocyte populations characterized by the lack of antigen-specific receptors. Sasaki et al. demonstrate the involvement of ILCs in the induction of diet-induced obesity. Specifically, they show that small intestinal ILC2s, but not white adipose tissue ILC2s, are involved in the induction of obesity.