Innate Lymphoid Cells in the Induction of Obesity

Takaharu Sasaki; Kazuyo Moro; Tetsuya Kubota; Naoto Kubota; Tamotsu Kato; Hiroshi Ohno; Susumu Nakae; Hirohisa Saito; Shigeo Koyasu

doi:10.1016/j.celrep.2019.06.016

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.

Authors

Takaharu Sasaki¹, Kazuyo Moro², Tetsuya Kubota³, Naoto Kubota³, Tamotsu Kato⁴, Hiroshi Ohno⁵, Susumu Nakae⁶, Hirohisa Saito⁷, Shigeo Koyasu⁸

Affiliations

¹ Laboratory for Innate Immune Systems, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan; Laboratory for Immune Cell Systems, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan; Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
² Laboratory for Innate Immune Systems, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan; Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan; Laboratory for Innate Immune Systems, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address: kazuyo.moro@riken.jp.
³ Laboratory for Metabolic Homeostasis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
⁴ Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan; Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan.
⁵ Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan; Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan; Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kanagawa, Japan.
⁶ Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁷ Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
⁸ Laboratory for Immune Cell Systems, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan; Deparment of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. Electronic address: shigeo.koyasu@riken.jp.

PMID: 31269440
DOI: 10.1016/j.celrep.2019.06.016

Abstract

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*

Substances

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