Targeting Th17 cells in autoimmune diseases

摘要

T helper 17 (Th17) cells have been implicated in the pathogenesis of most common autoimmune diseases, including psoriasis, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS). Although anti-interleukin-17 (IL-17) antibodies show marked clinical efficacy in psoriasis, targeting IL-17 alone is not sufficient to improve clinical end points in other autoimmune conditions, namely RA and Crohn's disease. Given that Th17 cells express IL-17 together with many other proinflammatory cytokines [IL-17F, IL-22, IL-26, and granulocyte-macrophage colony-stimulating factor (GM-CSF)], targeting the Th17 cell lineage may be superior to blocking a single effector cytokine. Here, we discuss the rationale for targeting two checkpoints in the development and inflammatory function of Th17 cells, retinoid-related orphan receptor-γt (RORγt) and IL-23, and we review recent progress in the development of both RORγt small molecule inhibitors and IL-23 neutralizing antibodies.