Kurzfassung

Psoriasis is a common inflammatory disease of the skin, manifested by hyperproliferative keratinocytes and massive infiltration of leukocytes. Protein expression of IL-17, IL-21 and IL-22 is increased in psoriatic skin lesions. In mice, IL-23-induced changes in the skin share many characteristics with human psoriasis, including erythema, acanthosis, parakeratosis, and leukocyte infiltration. These manifestations can be reproduced in mice treated by imiquimod (IMQ)-containing Aldara cream, or...Psoriasis is a common inflammatory disease of the skin, manifested by hyperproliferative keratinocytes and massive infiltration of leukocytes. Protein expression of IL-17, IL-21 and IL-22 is increased in psoriatic skin lesions. In mice, IL-23-induced changes in the skin share many characteristics with human psoriasis, including erythema, acanthosis, parakeratosis, and leukocyte infiltration. These manifestations can be reproduced in mice treated by imiquimod (IMQ)-containing Aldara cream, or in the K14/IL-17Aind mice that overexpress IL-17A specifically in the skin. We plan to use these two psoriasis models to study the role of Th17-related cytokines (IL-17 and IL-22) as well as of the pro-inflammatory cytokines IL-6, IL-1 and TNF in skin inflammation. A series of mice allowing for the deletion of the receptors of these cytokines will allow us to investigate their tissue-specific contribution to skin inflammation. Furthermore, using the K14/IL17Aind model, we want to delineate which innate or adaptive cell populations are pivotal in skin inflammation downstream of IL-17. Moreover, we want to investigate how IL-17 signaling regulates expansion of IL-17 expressing T cells and whether this is connected to spontaneous skin infections in mice lacking IL-17 signaling. Using these models, we aim to define the underlying cellular and molecular mechanisms governed by these cytokines in order to better understand the disease mechanisms and todesign better therapeutic approaches for psoriasis treatment in the future.» weiterlesen» einklappen