Mechanisms of Psoriatic Plaque Formation in Mice

Abstract

Psoriasis is an inflammatory skin disease of un known etiology. Dendritic cells (DC) are the key antigen-presenting cells of immune system with the capacity to balance (auto-)immunity and tolerance. Although DC have been implicated in psoriasis, their precise role in the pathogenesis of the disease remains thus far elusive. This has led us to further investigate and elucidate different cellular and molecular key mechanisms driving plaque formation. The research described in this thesis utilized the imiquimod (IMQ)-induced mouse model and generated a novel transgenic animal model, the DC-IL-17Aind strain, that is characterized by low level constitutive secretion of IL-17A. We used the IMQ mouse model to address the role of the different skin DC populations, including epidermal Langerhans cells, CD11b+ and Langerin+ dermal DC and plasmacytoid DC in the initiation of psoriatic skin lesions. In addition we addressed how the composition of the different myeloid cell populations changes during the course of IMQ-mediated psoriatic plaque formation and answered whether monocytes and their effector progeny are required for the initiation of skin disease. Finally we assessed the effects of constitutive expression of IL-17A at low level on epidermal homeostasis and skin immunity using the novel transgenic model, the DC-IL-17Aind mouse strain.