425 Immunomodulation of skin inflammation by P28GST, a helminth parasite-derived protein, in a murine model of psoriasis

The aim of this study was to investigate the therapeutic and immunomodulatory properties of P28GST in an experimental model of psoriasis. The potent anti-inflammatory and immunomodulatory properties of P28GST, a protein-derived from the schistosome helminth parasite, have been previously demonstrated in experimental colitis by our group and have recently led to a phase 2 clinical trial in Crohn’s disease patients. The therapeutic potential of P28GST was investigated in the murine model of psoriasis induced by daily application of Imiquimod during 5 days. Balb/C mice received a total of 3 subcutaneous injections of P28GST every 14 days, before induction of inflammation. P28GST efficacy was evaluated by using adapted PASI clinical score, Baker histological score, epidermal thickness measurement, analysis of skin and serum inflammation markers by qPCR and ELISA, and of immune response by flow cytometry. Treatment of mice by 3 injections of P28GST reduced skin inflammation induced by imiquimod, evidenced by significantly decreased PASI and Baker scores, with non- inferiority to a reference treatment by betamethasone. Significant decrease of mRNA encoding TNFα, IL1-β and Oncostatin M as well as increase of Arginase/ iNOS mRNA ratio indicated that P28GST induced a decrease of the Th1/Th17 inflammatory response associated to an increase of M2 anti-inflammatory macrophages, a hallmark of the Th2 –mediated regulatory response. These results extend the data observed in colitis to a skin inflammation model and confirm the capacity of this helminth -derived protein to induce a reequilibrium of the immune system paving the way to therapeutic applications.