¹Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany

Correspondence: Dr Karin Scharffetter-Kochanek, Department of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, Ulm D-89081, Germany. E-mail: karin.scharffetter-kochanek@uniklinik-ulm.de

Received 8 January 2006; Accepted 12 January 2006.

Abstract

The 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 ₂ integrin deficiency, one with a CD18 null mutation (CD18^-/-), and the other one with a hypomorphic CD18 mutation (CD18^hypo). 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-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 CD18^hypo 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.