ZFIN ID: ZDB-PUB-140524-8
Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fuelled matrix metalloproteinase production
Hall, C.J., Boyle, R.H., Sun, X., Wicker, S.M., Misa, J.P., Krissansen, G.W., Print, C.G., Crosier, K.E., Crosier, P.S.
Date: 2014
Source: Nature communications   5: 3880 (Journal)
Registered Authors: Crosier, Kathy, Hall, Chris
Keywords: none
Microarrays: GEO:GSE56365
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
PubMed: 24852213 Full text @ Nat. Commun.
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 &beta-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.