Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fuelled matrix metalloproteinase production.
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.
Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
Christopher J
CJ
Hall
Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
Rachel H
RH
Boyle
Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
Xueying
X
Sun
Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
Sophie M
SM
Wicker
Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
June P
JP
Misa
Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
Geoffrey W
GW
Krissansen
Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
Cristin G
CG
Print
Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
Kathryn E
KE
Crosier
Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
Philip S
PS
Crosier
D000818:Animals; D002465:Cell Movement; D003876:Dermatitis, Atopic / Q000473:pathology; D004195:Disease Models, Animal; D004817:Epidermis / Q000473:pathology*; D005227:Fatty Acids / Q000378:metabolism*; D020869:Gene Expression Profiling; D005938:Glucocorticoids / Q000378:metabolism; D007249:Inflammation / Q000473:pathology*; D007814:Larva / Q000382:microbiology; D007962:Leukocytes / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D060172:Morpholinos / Q000494:pharmacology; D020556:Neutrophil Infiltration / Q000187:drug effects; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins
D005227:Fatty Acids; D005938:Glucocorticoids; D060172:Morpholinos; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011965:Receptors, Glucocorticoid; D029961:Zebrafish Proteins; D020780:Matrix Metalloproteinase 9