title: UVB-induced skin inflammation and cutaneous tissue injury is dependent on the MHC class I-like protein, CD1d.
abstract: CD1d is a major histocompatibility complex class 1-like molecule that regulates the function and development of natural killer T (NKT) cells. Previously, we identified a critical role for the CD1d-NKT cell arm of innate immunity in promoting the development of UVB-induced p53 mutations, immune suppression, and skin tumors. Sunburn, an acute inflammatory response to UVB-induced cutaneous tissue injury, represents a clinical marker for non-melanoma skin cancer (NMSC) risk. However, the innate immune mechanisms controlling sunburn development are not considered relevant in NMSC etiology, and remain poorly investigated. Here we found that CD1d knockout (CD1d(-/-)) mice resist UVB-induced cutaneous tissue injury and inflammation compared with wild-type (WT) mice. This resistance was coupled with a faster epithelial tissue healing response. In contrast, the skins of UVB-irradiated invariant NKT cell-knockout (Jα18(-/-)) and NKT cell-deficient (TCRα(-/-)) mice, which express CD1d but are deficient in CD1d-dependent NKT cells, exhibited as much cutaneous tissue injury and inflammation as WT mice. In the absence of NKT cells, CD1d-deficient keratinocytes, dendritic cells, and macrophages exhibited diminished basal and stress-induced levels of pro-inflammatory mediators. Thus, our findings identify an essential role for CD1d in promoting UVB-induced cutaneous tissue injury and inflammation. They also suggest sunburn and NMSC etiologies are immunologically linked.
authors.affiliation: Department of Dermatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ryser
authors.affiliation: Galderma Research and Development, Les Templiers, Biot, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Schuppli
authors.affiliation: Galderma Research and Development, Les Templiers, Biot, France.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gauthier
authors.affiliation: Department of Dermatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
authors.forename: Dianelys R
authors.initials: DR
authors.lastname: Hernandez
authors.affiliation: Galderma Research and Development, Les Templiers, Biot, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Roye
authors.affiliation: Department of Dermatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hohl
authors.affiliation: Department of Lipid Nutrition, University of California, Davis, Davis, California, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: German
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Holzwarth
authors.affiliation: Department of Dermatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. Electronic address: angus.moodycliffe@chuv.ch.
authors.forename: Angus M
authors.initials: AM
authors.lastname: Moodycliffe
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology*; D003872:Dermatitis / Q000276:immunology* / Q000473:pathology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D013471:Sunburn / Q000276:immunology* / Q000473:pathology; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014945:Wound Healing / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; D015395:Histocompatibility Antigens Class I; D018836:Inflammation Mediators