Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fuelled matrix metalloproteinase production

Nat Commun. 2014 May 23;5:3880. doi: 10.1038/ncomms4880.

Abstract

In addition to satisfying the metabolic demands of cells, mitochondrial metabolism helps regulate immune cell function. To date, such cell-intrinsic metabolic-immunologic cross-talk has only been described operating in cells of the immune system. Here we show that epidermal cells utilize fatty acid β-oxidation to fuel their contribution to the immune response during cutaneous inflammation. By live imaging metabolic and immunological processes within intact zebrafish embryos during cutaneous inflammation, we uncover a mechanism where elevated β-oxidation-fuelled mitochondria-derived reactive oxygen species within epidermal cells helps guide matrix metalloproteinase-driven leukocyte recruitment. This mechanism requires the activity of a zebrafish homologue of the mammalian mitochondrial enzyme, Immunoresponsive gene 1. This study describes the first example of metabolic reprogramming operating within a non-immune cell type to help control its contribution to the immune response. Targeting of this metabolic-immunologic interface within keratinocytes may prove useful in treating inflammatory dermatoses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement*
  • Dermatitis, Atopic / pathology
  • Disease Models, Animal
  • Epidermis / pathology*
  • Fatty Acids / metabolism*
  • Gene Expression Profiling
  • Glucocorticoids / metabolism
  • Inflammation / pathology*
  • Larva / microbiology
  • Leukocytes / pathology*
  • Macrophages / metabolism
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Morpholinos / pharmacology
  • Neutrophil Infiltration / drug effects
  • Oxidation-Reduction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species
  • Receptors, Glucocorticoid / metabolism
  • Salmonella Infections, Animal / metabolism
  • Signal Transduction
  • Survival Analysis
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish Proteins

Substances

  • Fatty Acids
  • Glucocorticoids
  • Morpholinos
  • RNA, Messenger
  • Reactive Oxygen Species
  • Receptors, Glucocorticoid
  • Zebrafish Proteins
  • Matrix Metalloproteinase 9

Associated data

  • GEO/GSE56365