Extracellular adherence protein of Staphylococcus aureus suppresses disease by inhibiting T-cell recruitment in a mouse model of psoriasis

J Invest Dermatol. 2010 Mar;130(3):743-54. doi: 10.1038/jid.2009.310. Epub 2009 Oct 8.

Abstract

Psoriasis is a T-cell-mediated inflammatory disease. Previous studies focused on lymphocyte function-associated antigen 1 (LFA-1)-expressing T cells as a molecular target for therapeutic intervention. By contrast, information on therapeutic effects and the underlying mechanism of blocking the LFA-1 counter receptor, ICAM-1 is scarce. Here, we used the CD18 (beta2-integrin) hypomorphic (CD18hypo) mouse model of psoriasis to investigate the therapeutic role of extracellular adherence protein (Eap) of Staphylococcus aureus, which exerts antiinflammatory activities by interacting with the ICAM-1 function. We show that ICAM-1 is predominantly upregulated on endothelial cells in lesional skin of CD18hypo mice. In vitro Eap was found to disrupt cell-cell contacts between T cells and dendritic cells, and inhibit T-cell proliferation. By contrast, in vivo Eap rather blocked transmigration of T cells from vessels to inflamed skin of CD18hypo mice, but did not inhibit their proliferation and activation. Most importantly, Eap successfully suppressed the disease by blocking T-cell extravasation into the inflamed skin. Together, these data indicate that interaction between LFA-1 and ICAM-1 is causally involved in the pathogenesis of psoriasiform skin inflammation, and targeting ICAM-1 to selectively block T-cell extravasation by Eap without immune suppression may represent a potential therapeutic strategy for psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Bacterial Proteins / immunology
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / pharmacology*
  • CD18 Antigens / genetics
  • CD18 Antigens / immunology
  • Cell Communication / drug effects
  • Cell Communication / immunology
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / metabolism
  • Immunosuppressive Agents / pharmacology*
  • Intercellular Adhesion Molecule-1 / immunology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Phenotype
  • Psoriasis / drug therapy*
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • RNA-Binding Proteins / immunology
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / pharmacology*
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / immunology

Substances

  • Bacterial Proteins
  • CD18 Antigens
  • Eap-N protein, Staphylococcus aureus
  • Immunosuppressive Agents
  • RNA-Binding Proteins
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1