title: IL-27 Facilitates Skin Wound Healing through Induction of Epidermal Proliferation and Host Defense.
abstract: Skin wound repair requires a coordinated program of epithelial cell proliferation and differentiation as well as resistance to invading microbes. However, the factors that trigger epithelial cell proliferation in this inflammatory process are incompletely understood. In this study, we demonstrate that IL-27 is rapidly and transiently produced by CD301b+cells in the skin after injury. The functional role of IL-27 and CD301b+cells is demonstrated by the finding that CD301b-depleted mice exhibit delayed wound closure in vivo, which could be rescued by topical IL-27 treatment. Furthermore, genetic ablation of the IL-27 receptor (Il27Ra-/-) attenuates wound healing, suggesting an essential role for IL-27 signaling in skin regeneration in vivo. Mechanistically, IL-27 feeds back on keratinocytes to stimulate cell proliferation and re-epithelialization in the skin, whereas IL-27 leads to suppression of keratinocyte terminal differentiation. Finally, we identify that IL-27 potently increases expression of the antiviral oligoadenylate synthetase 2, but does not affect expression of antibacterial human beta defensin 2 or regenerating islet-derived protein 3-alpha. Together, our data suggest a previously unrecognized role for IL-27 in regulating epithelial cell proliferation and antiviral host defense during the normal wound healing response.
authors.affiliation: Department of Dermatology, Duke University School of Medicine, Durham, North Carolina, USA; Department of Dermatology, Wuhan General Hospital of Guangzhou Command, Wuhan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Jutamas
authors.initials: J
authors.lastname: Suwanpradid
authors.affiliation: Department of Dermatology, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sanchez-Lagunes
authors.affiliation: Department of Pathology, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Hae Woong
authors.initials: HW
authors.lastname: Choi
authors.affiliation: Department of Dermatology, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Hoang
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA; Department of Immunology, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Donghai
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pathology, Duke University School of Medicine, Durham, North Carolina, USA; Department of Immunology, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Soman N
authors.initials: SN
authors.lastname: Abraham
authors.affiliation: Department of Dermatology, Duke University School of Medicine, Durham, North Carolina, USA; Department of Immunology, Duke University School of Medicine, Durham, North Carolina, USA. Electronic address: Amanda.MacLeod@duke.edu.
authors.forename: Amanda S
authors.initials: AS
authors.lastname: MacLeod
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D064094:Interleukin-27 / Q000008:administration & dosage / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000235:genetics*; D018123:Receptors, Interleukin; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000502:physiology*
chemical_list: C484747:Il27ra protein, mouse; D064094:Interleukin-27; D037181:Lectins, C-Type; C464940:MGL2 protein, mouse; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin