Gradual development of psoriatic skin lesions by constitutive low-level expression of IL-17A

Psoriasis is a common chronic inflammatory skin disease restricted to humans. The understanding of its pathogenesis has long been hampered by the lack of suitable chronic mouse models. The cytokine IL-17A has emerged as a key player in epithelial immune responses and the defense against extracellular pathogens. Moreover, enhanced expression of IL-17A can turn pathologic and is closely associated with psoriasis. In this study, we generated a novel transgenic mouse model that recapitulates many characteristics of psoriasis. DC-1L-17A(ind) mice with constitutive low-level expression of IL-17A by CD11c(+) cells gradually develop skin lesions during adult life. The lesions preferentially occur at sites of mechanical stress and exhibit macroscopic, histologic and genetic hallmarks of psoriatic plaques. Intriguingly, the age of disease onset depends on the levels of IL-17A and disruption of the epidermal barrier by tape-stripping triggers psoriatic plaque formation in the DC-1L-17A(in) model. In summary, our results suggest that deregulated IL-17A together with epidermal trauma initiates skin inflammation and lesion formation in mice closely resembling plaque-type psoriasis. Due to the gradual development and chronic nature of disease, DC-IL-17(ind) mice provide a unique tool to dissect the pathogenesis of human psoriasis and potentially could serve as a model to validate novel therapeutic strategies. (C) 2015 Elsevier Inc. All rights reserved.