S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3

Immunity. 2013 Dec 12;39(6):1171-81. doi: 10.1016/j.immuni.2013.11.011.


Psoriasis is a common heterogeneous inflammatory skin disease with a complex pathophysiology and limited treatment options. Here we performed proteomic analyses of human psoriatic epidermis and found S100A8-S100A9, also called calprotectin, as the most upregulated proteins, followed by the complement component C3. Both S100A8-S100A9 and C3 are specifically expressed in lesional psoriatic skin. S100A9 is shown here to function as a chromatin component modulating C3 expression in mouse and human cells by binding to a region upstream of the C3 start site. When S100A9 was genetically deleted in mouse models of skin inflammation, the psoriasis-like skin disease and inflammation were strongly attenuated, with a mild immune infiltrate and decreased amounts of C3. In addition, inhibition of C3 in the mouse model strongly reduced the inflammatory skin disease. Thus, S100A8-S100A9 can regulate C3 at the nuclear level and present potential new therapeutic targets for psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calgranulin A / genetics
  • Calgranulin A / metabolism*
  • Calgranulin B / genetics
  • Calgranulin B / metabolism*
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Complement C3 / genetics*
  • Complement C3 / metabolism
  • Disease Models, Animal
  • Epidermal Cells
  • Epidermis / immunology
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Proteome
  • Psoriasis / genetics*
  • Psoriasis / immunology
  • Psoriasis / physiopathology*
  • RNA, Small Interfering / metabolism


  • Calgranulin A
  • Calgranulin B
  • Complement C3
  • Proteome
  • RNA, Small Interfering