Skin Patterning in Psoriasis by Spatial Interactions between Pathogenic Cytokines

Abstract

Summary: Disorders of human skin manifest themselves with patterns of lesions ranging from simple scattered spots to complex rings and spirals. These patterns are an essential characteristic of skin disease, yet the mechanisms through which they arise remain unknown. Here we show that all known patterns of psoriasis, a common inflammatory skin disease, can be explained in terms of reaction-diffusion. We constructed a computational model based on the known interactions between the main pathogenic cytokines: interleukins IL-17 and IL-23, and tumor necrosis factor TNF-α. Simulations revealed that the parameter space of the model contained all classes of psoriatic lesion patterns. They also faithfully reproduced the growth and evolution of the plaques and the response to treatment by cytokine targeting. Thus the pathogenesis of inflammatory diseases, such as psoriasis, may be readily understood in the framework of the stimulatory and inhibitory interactions between a few diffusing mediators. : Dermatology; Biological Sciences; in silico biology Subject Areas: Dermatology, Biological Sciences, in silico biology