title: CD18 in monogenic and polygenic inflammatory processes of the skin.
abstract: The beta 2 integrin family (CD11/CD18) of leukocyte adhesion molecules plays a key role in inflammation. Absence of the common chain (CD18) leads to leukocyte adhesion deficiency-1 (LAD1) in humans. We here summarize data of two genetically defined mice models of beta 2 integrin deficiency, one with a CD18 null mutation (CD18-/-), and the other one with a hypomorphic CD18 mutation (CD18hypo). Firstly, we focus on the underlying mechanism of a severely impaired wound healing in CD18-/- mice, outlining a scenario in which a defective extravasation and phagocytosis of CD18-/- neutrophils results in delayed myofibroblast-dependent wound contraction owing to a deficient transforming growth factor-beta 1 release. Based on this, we have identified a potential therapy that fully rescued the impaired wound healing in CD18-/- mice. Secondly, we expand on a CD18hyp0 PL/J mouse model closely resembling human psoriasis. Apart from common clinical and pathophysiological features, this psoriasiform dermatitis also depends on the presence of activated CD4+ T cells. We here recapitulate the influence of a reduced CD18 gene expression on T-cell function, also with regard to CD18 gene-dose effects, and its contribution to the pathogenesis of this disease. Taken together, these unique features make this model a valuable tool for investigations into the pathogenesis of human psoriasis--including its polygenic base--and future preclinical studies.
authors.affiliation: Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Peters
authors.forename: Anca
authors.initials: A
authors.lastname: Sindrilaru
authors.forename: Honglin
authors.initials: H
authors.lastname: Wang
authors.forename: Tsvetelina
authors.initials: T
authors.lastname: Oreshkova
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Renkl
authors.forename: Daniel
authors.initials: D
authors.lastname: Kess
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000502:physiology*; D002454:Cell Differentiation; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D051379:Mice; D011565:Psoriasis / Q000209:etiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D053773:Transforming Growth Factor beta1; D014945:Wound Healing
chemical_list: D018821:CD18 Antigens; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1