The IL-1 family in relation to psoriasis

摘要: Psoriasis is a common chronic inflammatory skin disease which can also affect the joints. Its pathogenesis still to be fully elucidated and involves wide range of mediators, tissue immune cells. At present, there no treatment available cure psoriasis. Although biologics have considerably improved most severe cases pressing clinical need improve therapy for specific subtypes (e.g. pustular psoriasis) vast majority patients suffering from psoriasis classified as mild moderate. In particular, efficient well tolerated topical approaches are lacking. This work has focused 1) on advancing our understanding IL-36 cytokines recognised their significance in psoriasis, 2) identifying endogenous limiting mediators such IL-18 binding protein how they could manipulated therapeutic approach 3) IL-17 neutralising RNA aptamers tools therapy. Main results include identification biologic activity processed non-processed members. N-terminal cleavage required increase all The protease responsible IL-36RA processing was elucidated. Neutrophil proteases kallikrein 7 cleave pro-inflammatory However, second step seems necessary full activation potentially aminopeptidase remains identified. Secondly, it found that human primary fibroblasts produce significant levels IL-18BP, controls function IL-18. Endogenous IL-18BP induced by IL-27 which, when given combination with hydrocortisone does not induce responses. Thirdly, an aptamer verified block IL-17A fibroblast Th17 co-cultures but keratinocyte cultures. Significant uptake keratinocytes identified lack capacity.