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

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

Author information

1
BBVA Foundation-CNIO Cancer Cell Biology Programme, Spanish National Cancer Research Centre (CNIO), 29029 Madrid, Spain.
2
Proteomics Unit, Spanish National Cancer Research Centre (CNIO), 29029 Madrid, Spain.
3
Department of Dermatology, Hospital Universitario La Princesa, 28006 Madrid, Spain.
4
Leukocyte Adhesion Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY, UK.
5
BBVA Foundation-CNIO Cancer Cell Biology Programme, Spanish National Cancer Research Centre (CNIO), 29029 Madrid, Spain. Electronic address: ewagner@cnio.es.

Abstract

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.

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PMID:
24332034
DOI:
10.1016/j.immuni.2013.11.011
[Indexed for MEDLINE]
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