CD18 in monogenic and polygenic inflammatory processes of the skin.
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.
Peters
Thorsten
T
Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.
Sindrilaru
Anca
A
Wang
Honglin
H
Oreshkova
Tsvetelina
T
Renkl
Andreas C
AC
Kess
Daniel
D
Scharffetter-Kochanek
Karin
K
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
D018821:CD18 Antigens; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1