IL-17 and IL-17R: an auspicious therapeutic target for psoriatic disease

Abstract The continuous discovery of new T cell subpopulations in human autoimmune diseases is making the immunopathological network more complex. Th17 cells are one such newly identified subset of T cells, characterized by the production of signature cytokine IL-17. In last few years, several studies have strongly established the regulatory role of Th17 cells and its signature cytokine IL-17 in autoimmune diseases including psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus and multiple sclerosis. Psoriasis and PsA are immune mediated hyperproliferative diseases, affecting skin and joint respectively. Before the discovery of Th17 cells, psoriasis and psoriatic diseases were thought to be chiefly Th1 mediated diseases; later on IL-17 knockout animal studies as well as human experimental data indicate the crucial role of Th17 cells and its signature cytokine IL-17 in the pathogenesis of these diseases. In vitro human studies have shown the abundance of Th17 cells in the psoriatic plaques. Subsequently our research group has extended this observation in psoriatic arthritis and found the abundance of CD4+IL-17+ T cells in the synovial fluid and majority of these T cells are of memory phenotype (CD4RO+CD45RA-CD11a+). In addition, we showed the significant presence of functional IL-17 receptor in synovial fibroblast of psoriatic arthritis patients. Considering the strong association of IL-17 and psoriatic disease, IL-17 targeted therapy have shown promises in preclinical and clinical trials. In this review article, we have discussed the pathogenic role of IL-17 in psoriatic disease and summarized the therapeutic efficacy and safety profile of different anti IL-17 therapy as an anti-psoriatic agent.