title: Targeting Th17 cells in autoimmune diseases.
abstract: 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.
authors.affiliation: Tempero Pharmaceuticals, A GSK Company, Cambridge, MA 02139, USA. Electronic address: jianfeiyang2012@gmail.com.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sundrud
authors.affiliation: Tempero Pharmaceuticals, A GSK Company, Cambridge, MA 02139, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Skepner
authors.affiliation: Tempero Pharmaceuticals, A GSK Company, Cambridge, MA 02139, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamagata
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D016503:Drug Delivery Systems; D006801:Humans; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000037:antagonists & inhibitors / Q000276:immunology; D054852:Small Molecule Libraries / Q000494:pharmacology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology*
chemical_list: D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D054852:Small Molecule Libraries
keywords: IL-17; IL-23; RORγt; autoimmune diseases