PD-1 Is Involved in the Dysregulation of Type 2 Innate Lymphoid Cells in a Murine Model of Obesity

Cell Rep. 2018 Nov 20;25(8):2053-2060.e4. doi: 10.1016/j.celrep.2018.10.091.

Abstract

Recent observations clearly highlight the critical role of type 2 innate lymphoid cells in maintaining the homeostasis of adipose tissues in humans and mice. This cell population promotes beiging and limits adiposity directly and indirectly by sustaining a Th2-prone environment enriched in eosinophils and alternatively activated macrophages. Accordingly, the number and function of type 2 innate lymphoid cells (ILC2s) are strongly impaired in obese individuals. In this work, we identify the PD-1-PD-L1 pathway as a factor leading to ILC2 destabilization upon high-fat feeding resulting in impaired tissue metabolism. Tumor necrosis factor (TNF) appears to play a central role, triggering interleukin-33 (IL-33)-dependent PD-1 expression on ILC2s and recruiting and activating PD-L1hi M1 macrophages. PD-1 blockade partially restores the type 2 innate axis, raising the possibility of restoring tissue homeostasis.

Keywords: IL-33; ILC2; PD-1; PD-L1; TNF; adipose tissue; innate lymphoid cells; macrophage; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, High-Fat
  • Disease Models, Animal
  • Eosinophils / metabolism
  • Homeostasis
  • Immunity, Innate*
  • Inflammation / pathology
  • Interleukin-33 / metabolism
  • Lymphocytes / metabolism*
  • Macrophage Activation
  • Macrophages / metabolism
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / immunology*
  • Obesity / metabolism*
  • Programmed Cell Death 1 Receptor / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • Interleukin-33
  • Programmed Cell Death 1 Receptor
  • Tumor Necrosis Factor-alpha