UVB-induced skin inflammation and cutaneous tissue injury is dependent on the MHC class I-like protein, CD1d

Stephan Ryser, Marlène Schuppli, Beatrice Gauthier, Dianelys R. Hernandez, Olivier Roye, Daniel Hohl, Bruce German, James A. Holzwarth, Angus M. Moodycliffe

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)192-202
Number of pages11
JournalJournal of Investigative Dermatology
Volume134
Issue number1
DOIs
StatePublished - Jan 2014

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Ryser, S., Schuppli, M., Gauthier, B., Hernandez, D. R., Roye, O., Hohl, D., German, B., Holzwarth, J. A., & Moodycliffe, A. M. (2014). UVB-induced skin inflammation and cutaneous tissue injury is dependent on the MHC class I-like protein, CD1d. Journal of Investigative Dermatology, 134(1), 192-202. https://doi.org/10.1038/jid.2013.300