title: Dendritic cell-epithelium interplay is a determinant factor for corneal epithelial wound repair.
abstract: The functions of intraepithelial dendritic cells (DCs) are critical for mucosal innate and adaptive immunity, but little is known about the role of tissue-specific DCs in epithelial homeostasis and tissue repair. By using the epithelial debridement wound model and CD11c-diphtheria toxin receptor mice that express a CD11c promoter-driven diphtheria toxin receptor, we showed that DCs migrate along with the epithelial sheet to cover the wound and that local depletion of DCs resulted in a significant delay in epithelial wound closure. In response to wounding, migratory epithelia produce CXCL10, thymic stromal lymphopoietin, and IL-1β and its antagonist soluble IL-1 receptor antagonist (sIL-1Ra); depletion of corneal DCs reversed their elevated expressions to a different extent, suggesting a DC-mediated positive feedback loop in epithelial gene expression. Furthermore, both CXCL10 and thymic stromal lymphopoietin were localized in migratory epithelia, suggesting that epithelial cells play a key role in DC infiltration and activation in injured corneas. On the other hand, DC depletion resulted in suppressed epithelial AKT activation, increased cell apoptosis, and decreased polymorphonuclear leukocyte infiltration in the healing cornea. These results indicate that DCs and epithelium form a functional entity at mucosal surfaces for maintaining corneal homeostasis and for tissue repair.
authors.affiliation: Department of Ophthalmology, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Gao
authors.forename: Jia
authors.initials: J
authors.lastname: Yin
authors.forename: Gi Sang
authors.initials: GS
authors.lastname: Yoon
authors.forename: Qing-Sheng
authors.initials: QS
authors.lastname: Mi
authors.forename: Fu-Shin X
authors.initials: FS
authors.lastname: Yu
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003315:Cornea / Q000166:cytology; D065306:Corneal Injuries; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D019573:Epithelium, Corneal / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D020556:Neutrophil Infiltration / Q000502:physiology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D015398:Signal Transduction; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016207:Cytokines; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D058539:Phosphatidylinositol 3-Kinase