Type-2 innate lymphoid cells control the development of atherosclerosis in mice

Nat Commun. 2017 Jun 7:8:15781. doi: 10.1038/ncomms15781.

Abstract

Type-2 innate lymphoid cells (ILC2) are a prominent source of type II cytokines and are found constitutively at mucosal surfaces and in visceral adipose tissue. Despite their role in limiting obesity, how ILC2s respond to high fat feeding is poorly understood, and their direct influence on the development of atherosclerosis has not been explored. Here, we show that ILC2 are present in para-aortic adipose tissue and lymph nodes and display an inflammatory-like phenotype atypical of adipose resident ILC2. High fat feeding alters both the number of ILC2 and their type II cytokine production. Selective genetic ablation of ILC2 in Ldlr-/- mice accelerates the development of atherosclerosis, which is prevented by reconstitution with wild type but not Il5-/- or Il13-/- ILC2. We conclude that ILC2 represent a major innate cell source of IL-5 and IL-13 required for mounting atheroprotective immunity, which can be altered by high fat diet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / pathology
  • Animals
  • Aorta / metabolism
  • Aorta / pathology
  • Atherosclerosis / etiology
  • Atherosclerosis / pathology*
  • Bone Marrow Transplantation
  • Cytokines / metabolism
  • Diet, High-Fat / adverse effects
  • Female
  • Interleukin-13 / metabolism
  • Interleukin-5 / metabolism
  • Lymphocytes / metabolism
  • Lymphocytes / pathology*
  • Mice, Knockout, ApoE
  • Mice, Mutant Strains
  • Plaque, Atherosclerotic / pathology

Substances

  • Cytokines
  • Interleukin-13
  • Interleukin-5