The search for pathogenic T cells and the genetic basis of psoriasis using a severe combined immunodeficient mouse...

The immunologic and genetic bases of psoriasis are under active investigation throughout the world. Rather than pursue the genetic linkage to psoriasis to discover the gene(s) responsible for causing the disease, we have focused on the cellular immunology and basic biology using a novel animal model. We reasoned by identifying specific cellular and molecular abnormalities involved in the biologic responses that initiate lesion formation, that the genes involved in such a pathologic process would lead us to the correct causative DNA-based abnormality that determines disease susceptibility and inheritance. To pursue this line of inquiry, we utilized an animal model in which severe combined immunodeficient (SCID) mice were engrafted with symptomless skin (PN skin), and bona fide psoriatic plaques (PP skin) were created using specific pathogenic T cell subsets. This model can be used experimentally not only to study the mechanism by which PP skin is converted to PN skin, but also to create PP skin from PN skin. The clinical, histologic, immunologic, and pharmacologic validation of this SCID mouse model will be presented. This summary will also highlight the value of such a model, which has recently led to the discovery of previously overlooked types of immunocytes that are associated with induction of psoriatic lesions. Finally, a novel hypothesis linking the immunology and the genetics of psoriasis, based on findings using this animal model, will conclude this presentation.