title: IL-22 promotes fibroblast-mediated wound repair in the skin.
abstract: Skin wound repair requires complex and highly coordinated interactions between keratinocytes, fibroblasts, and immune cells to restore the epidermal barrier and tissue architecture after acute injury. The cytokine IL-22 mediates unidirectional signaling from immune cells to epithelial cells during injury of peripheral tissues such as the liver and colon, where IL-22 causes epithelial cells to produce antibacterial proteins, express mucins, and enhance epithelial regeneration. In this study, we used IL-22(-/-) mice to investigate the in vivo role for IL-22 in acute skin wounding. We found that IL-22(-/-) mice displayed major defects in the skin's dermal compartment after full-thickness wounding. We also found that IL-22 signaling is active in fibroblasts, using in vitro assays with primary fibroblasts, and that IL-22 directs extracellular matrix (ECM) gene expression and myofibroblast differentiation both in vitro and in vivo. These data define roles of IL-22 beyond epithelial cross talk, and suggest that IL-22 has a previously unidentified role in skin repair by mediating interactions between immune cells and fibroblasts.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: McGee
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Schmidt
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Booth
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: Sean
authors.initials: S
authors.lastname: Stevens
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Valerie
authors.initials: V
authors.lastname: Horsley
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology*; D007378:Interleukins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D058628:Myofibroblasts / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000293:injuries* / Q000503:physiopathology*; D014945:Wound Healing / Q000502:physiology*; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D012333:RNA, Messenger; D000097043:Interleukin-22