Gene from a psoriasis susceptibility locus primes the skin for inflammation

Research output: Contribution to journalResearch articleContributedpeer-review


  • Ronald Wolf - , National Institutes of Health (NIH), Ludwig Maximilian University of Munich (Author)
  • Francesca Mascia - , National Institutes of Health (NIH) (Author)
  • Alif Dharamsi - , National Institutes of Health (NIH) (Author)
  • O. M.Zack Howard - , National Institutes of Health (NIH) (Author)
  • Christophe Cataisson - , National Institutes of Health (NIH) (Author)
  • Val Bliskovski - , National Institutes of Health (NIH) (Author)
  • Jason Winston - , National Institutes of Health (NIH) (Author)
  • Lionel Feigenbaum - , SAIC (Author)
  • Ulrike Lichti - , National Institutes of Health (NIH) (Author)
  • Thomas Ruzicka - , Ludwig Maximilian University of Munich (Author)
  • Triantafyllos Chavakis - , Department of internal Medicine 3, Institute of Physiology, National Institutes of Health (NIH) (Author)
  • Stuart H. Yuspa - , National Institutes of Health (NIH) (Author)


Psoriasis is a common complex genetic disease characterized by hyperplasia and inflammation in the skin; however, the relative contributions of epidermal cells and the immune system to disease pathogenesis remain unclear. Linkage studies have defined a psoriasis susceptibility locus (PSORS4) on 1q21, the epidermal differentiation complex, which includes genes for small S100 calcium-binding proteins. These proteins are involved in extracellular and intracellular signaling during epithelial host defense, linking innate and adaptive immunity. Inflammation-prone psoriatic skin constitutively expresses elevated concentrations of S100A7 (psoriasin) and S100A15 (koebnerisin) in the epidermis. Here, we report that genetically modified mice expressing elevated amounts of doxycycline-regulated mS100a7a15 in skin keratinocytes demonstrated an exaggerated inflammatory response when challenged by exogenous stimuli such as abrasion (Koebner phenomenon). This immune response was characterized by immune cell infiltration and elevated concentrations of T helper 1 (T H1) and TH17 proinflammatory cytokines, which have been linked to the pathogenesis of psoriasis and were further amplified upon challenge. Both inflammation priming and amplification required mS100a7a15 binding to the receptor of advanced glycation end products (RAGE). mS100a7a15 potentiated inflammation by acting directly as a chemoattractant for leukocytes, further increasing the number of inflammatory cells infiltrating the skin. This study provides a pathogenetic psoriasis model using a psoriasis candidate gene to link the epidermis and innate immune system in inflammation priming, highlighting the S100A7A15-RAGE axis as a potential therapeutic target.


Original languageEnglish
Article number61ra90
JournalScience Translational Medicine
Issue number61
Publication statusPublished - 8 Dec 2010

External IDs

researchoutputwizard legacy.publication#36907
Scopus 78650183999
PubMed 21148126


ASJC Scopus subject areas