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Investigating the role of dysregulated Interleukin-17 signalling in the pathogenesis of psoriasis


Psoriasis is the most prevalent autoimmune disease, affecting approximately 125 million people worldwide. In Ireland alone it costs the health care system approximately 30 million euro yearly. Psoriasis is characterised by inflamed scaly red psoriatic plaques on the epidermis of sufferers and 20% of patients develop severe psoriasis, which is associated with an increased risk of cardiovascular disease and metabolic syndrome. Psoriasis can also be detrimental to a patient's psychological well-being. As there is no cure a psoriasis patient has a life-long struggle with managing the disease.
Anti-Interleukin-17 (IL-17) biologics that target IL-17A and IL-17 receptor A have proved successful in clinical trials in treating psoriasis, however, how IL-17 cytokines mediate the inflammatory effects in psoriasis pathogenesis remains incompletely understood. These biologic therapies, though highly efficacious, will remain unavailable to the majority of psoriasis patients due to their expense. New research findings suggest that there are more suitable therapeutic targets amongst the IL-17 cytokine and receptor families, which may not be as critical to the host’s response to infection, emphasising a need for new therapeutic strategies.
We propose to characterise the physiological role of IL-17 receptor D in psoriasis pathogenesis and present preliminary data to suggest that this role is protective. We also propose, with supporting data, that IL-17C may contribute to psoriasis pathogenesis by activating the IL-1 inflammasome and IL-17RD may regulate this. We propose to use a psoriasiform disease model in Il-17rd-deficient mice to characterise its function and samples from psoriasis patients to isolate primary keratinocytes to dissect IL-17C signalling pathways.
Determining the roles of IL-17C and IL-17RD will aid in finally treating psoriasis effectively and would also aid in comprehending the role of dysregulated IL-17 signalling in other chronic inflammatory diseases.

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University of Zurich
Ramistrasse 71
8006 Zurich

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Higher or Secondary Education Establishments
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Lars French (Prof.)
€ 207 928,80