Extracellular Adherence Protein of Staphylococcus aureus Suppresses Disease by Inhibiting T-Cell Recruitment in a Mouse Model of Psoriasis

• Published in: Journal of investigative dermatology Vol. 130; no. 3; pp. 743 - 754
• Main Authors: Wang, Honglin, von Rohrscheidt, Julia, Roehrbein, Jan, Peters, Thorsten, Sindrilaru, Anca, Kess, Daniel, Preissner, Klaus T., Scharffetter-Kochanek, Karin
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2010; Nature Publishing Group; Elsevier Limited
• Subjects: Adoptive Transfer; Animals; Bacterial diseases; Bacterial Proteins - immunology; Bacterial Proteins - metabolism; Bacterial Proteins - pharmacology; Biological and medical sciences; 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; Dermatology; Disease Models, Animal; Human bacterial diseases; Immunosuppressive Agents - immunology; Immunosuppressive Agents - metabolism; Immunosuppressive Agents - pharmacology; Infectious diseases; Intercellular Adhesion Molecule-1 - immunology; Intercellular Adhesion Molecule-1 - metabolism; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Phenotype; Psoriasis - drug therapy; Psoriasis - immunology; Psoriasis - pathology; Psoriasis. Parapsoriasis. Lichen; RNA-Binding Proteins - immunology; RNA-Binding Proteins - metabolism; RNA-Binding Proteins - pharmacology; Skin - immunology; Skin - metabolism; Skin - pathology; Staphylococcal infections, streptococcal infections, pneumococcal infections; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation - immunology; Skin disease; Psoriasis; Dermatology; Rodentia; Adhesion; Extracellular; Protein; Recruitment; Infection; Vertebrata; Mammalia; Mouse; Animal; T-Lymphocyte; Bacteriosis; Bacteria; Micrococcales; Micrococcaceae; Models; Staphylococcal infection; Staphylococcus aureus
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2009.310

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 (β2-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.