title: Extracellular adherence protein of Staphylococcus aureus suppresses disease by inhibiting T-cell recruitment in a mouse model of psoriasis.
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.
authors.affiliation: Shanghai Institute of Immunology, Institute of Medicine Science, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Wang
authors.forename: Julia
authors.initials: J
authors.lastname: von Rohrscheidt
authors.forename: Jan
authors.initials: J
authors.lastname: Roehrbein
authors.forename: Thorsten
authors.initials: T
authors.lastname: Peters
authors.forename: Anca
authors.initials: A
authors.lastname: Sindrilaru
authors.forename: Daniel
authors.initials: D
authors.lastname: Kess
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D018821:CD18 Antigens; C444739:Eap-N protein, Staphylococcus aureus; D007166:Immunosuppressive Agents; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1