PUBLICATION
Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fuelled matrix metalloproteinase production
- Authors
- 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.
- ID
- ZDB-PUB-140524-8
- Date
- 2014
- Source
- Nature communications 5: 3880 (Journal)
- Registered Authors
- Crosier, Kathy, Hall, Chris
- Keywords
- none
- Datasets
- GEO:GSE56365
- MeSH Terms
-
- Oxidation-Reduction
- Zebrafish/embryology
- Zebrafish/genetics
- Larva/microbiology
- Leukocytes/pathology*
- PubMed
- 24852213 Full text @ Nat. Commun.
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 &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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping