title: Involvement of an NKG2D ligand H60c in epidermal dendritic T cell-mediated wound repair.
abstract: Dendritic epidermal T cells (DETCs) found in mouse skin are NKG2D-positive γδ T cells involved in immune surveillance and wound repair. It is assumed that the interaction of an NKG2D receptor on DETCs and an MHC class I-like NKG2D ligand on keratinocytes activates DETCs, which then secrete cytokines promoting wound repair. However, direct evidence that DETC activation through NKG2D signaling promotes wound repair is not available. In the present study, we generated mAbs for an NKG2D ligand H60c previously suggested to be expressed specifically on skin keratinocytes. Local administration of H60c-specific mAb inhibited activation of DETCs and significantly delayed wound repair. Likewise, administration of NKG2D-specific mAb impaired wound repair to a similar extent. The delay in wound closure resulting from the blockade of the NKG2D pathway was comparable to that observed in γδ T cell-deficient mice. These results indicate that H60c/NKG2D interactions play a critical role in wound repair. Reassessment of binding affinities showed that H60c monomers bind to NKG2D with affinity (K(d) = 26 ± 3.2 nM) comparable to those of other high-affinity NKG2D ligands. H60c is transcribed not only in skin but also in tissues such as tongue and female reproductive tract known to contain epithelium-resident γδ T cells expressing invariant TCRs, suggesting a more general role for H60c in the maintenance of epithelial integrity.
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yoshida
authors.forename: Rania Hassan
authors.initials: RH
authors.lastname: Mohamed
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kajikawa
authors.forename: Jun
authors.initials: J
authors.lastname: Koizumi
authors.forename: Minami
authors.initials: M
authors.lastname: Tanaka
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fugo
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Otsuka
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Chiba
authors.forename: Masanori
authors.initials: M
authors.lastname: Kasahara
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002450:Cell Communication; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004817:Epidermis; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens / Q000276:immunology* / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014945:Wound Healing / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; C527293:H60c protein, mouse; C527086:Klrk1 protein, mouse; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K