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

• Published in: Nature communications Vol. 5; no. 1; p. 3880
• Main Authors: Hall, Christopher J., Boyle, Rachel H., Sun, Xueying, Wicker, Sophie M., Misa, June P, Krissansen, Geoffrey W., Print, Cristin G., Crosier, Kathryn E., Crosier, Philip S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-05-2014; Nature Publishing Group
• Subjects: 13/31; 13/51; 14/19; 14/32; 38/32; 38/39; 38/61; 38/77; 631/250/1933; 631/250/256; 631/443/319; 64/116; 64/60; Animals; Cell Movement; Dermatitis, Atopic - pathology; Disease Models, Animal; Epidermis - pathology; Fatty Acids - metabolism; Gene Expression Profiling; Glucocorticoids - metabolism; Humanities and Social Sciences; Inflammation - pathology; Larva - microbiology; Leukocytes - pathology; Macrophages - metabolism; Matrix Metalloproteinase 9 - metabolism; Mice; Mitochondria - drug effects; Mitochondria - metabolism; Morpholinos - pharmacology; multidisciplinary; Neutrophil Infiltration - drug effects; Oxidation-Reduction; Reactive Oxygen Species; Receptors, Glucocorticoid - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Salmonella Infections, Animal - metabolism; Science; Science (multidisciplinary); Signal Transduction; Survival Analysis; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms4880

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.
Metabolic regulation is emerging as an important component of immune response control and may be implicated in the development of inflammatory diseases. Here, the authors show that inflammatory leukocyte recruitment depends on mitochondrial metabolism in epidermal cells in zebrafish.