Visceral Adipose Tissue Immune Homeostasis Is Regulated by the Crosstalk between Adipocytes and Dendritic Cell Subsets

Cell Metab. 2018 Mar 6;27(3):588-601.e4. doi: 10.1016/j.cmet.2018.02.007.

Abstract

Visceral adipose tissue (VAT) has multiple roles in orchestrating whole-body energy homeostasis. In addition, VAT is now considered an immune site harboring an array of innate and adaptive immune cells with a direct role in immune surveillance and host defense. We report that conventional dendritic cells (cDCs) in VAT acquire a tolerogenic phenotype through upregulation of pathways involved in adipocyte differentiation. While activation of the Wnt/β-catenin pathway in cDC1 DCs induces IL-10 production, upregulation of the PPARγ pathway in cDC2 DCs directly suppresses their activation. Combined, they promote an anti-inflammatory milieu in vivo delaying the onset of obesity-induced chronic inflammation and insulin resistance. Under long-term over-nutrition, changes in adipocyte biology curtail β-catenin and PPARγ activation, contributing to VAT inflammation.

Keywords: Pparγ; adipose tissue; dendritic cells; diabetes; homeostasis; inflammation; insulin resistance; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Animals
  • Cell Differentiation
  • Dendritic Cells / metabolism*
  • Homeostasis / immunology*
  • Inflammation / immunology
  • Insulin Resistance / immunology
  • Interleukin-10 / immunology
  • Intra-Abdominal Fat / immunology*
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Obesity / metabolism*
  • PPAR gamma / immunology
  • Wnt Signaling Pathway

Substances

  • IL10 protein, mouse
  • PPAR gamma
  • Interleukin-10