title: Deficiency of both L-selectin and ICAM-1 exacerbates imiquimod-induced psoriasis-like skin inflammation through increased infiltration of antigen presenting cells.
abstract: To assess the role of inter-cellular adhesion molecule (ICAM)-1 and L-selectin in psoriasis pathogenic process, we examined the psoriasiform skin inflammation triggered by imiquimod, a toll-like receptor 7/8 agonist, in mice lacking ICAM-1 (ICAM-1(-/-)), L-selectin (L-selectin(-/-)), or both (L-selectin/ICAM-1(-/-)). Disease severity was significantly reduced in ICAM-1(-/-) and L-selectin(-/-) mice compared with wild type mice, while it was exacerbated in L-selectin/ICAM-1(-/-) mice. Cutaneous interleukin (IL)-17A, IL-23, and tumor necrosis factor (TNF)-α expression was increased in L-selectin/ICAM-1(-/-) mice compared with wild type mice. Furthermore, only L-selectin/ICAM-1(-/-) mice was refractory to anti-TNF-α antibody treatment. The skin lesion from L-selectin/ICAM-1(-/-) mice showed augmented E-selectin expression compared with ICAM-1(-/-) and L-selectin(-/-) mice, and augmented E-selectin ligand-1 expression compared with wild type mice. The current study demonstrates that although ICAM-1 and L-selectin regulate psoriasiform inflammation, deleting both L-selectin and ICAM-1 simultaneously would rather induce refractory skin inflammation, due to compensatory up-regulation of other adhesion molecules.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Mitsui
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan. Electronic address: ytada-tky@umin.ac.jp.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kamata
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: Carren
authors.initials: C
authors.lastname: Hau
authors.affiliation: Department of Dermatology, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Asahina
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan. Electronic address: satos-der@h.u-tokyo.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002465:Cell Movement; D000077271:Imiquimod; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000276:immunology; D020381:Interleukin-17 / Q000378:metabolism; D019041:L-Selectin / Q000235:genetics* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011565:Psoriasis / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D012867:Skin / Q000503:physiopathology*
chemical_list: D000634:Aminoquinolines; D020381:Interleukin-17; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D000077271:Imiquimod
keywords: Adhesion molecules; Cytokine; Skin