Targeting Th17 cells in autoimmune diseases
J Yang, MS Sundrud, J Skepner, T Yamagata - Trends in pharmacological …, 2014 - cell.com
J Yang, MS Sundrud, J Skepner, T Yamagata
Trends in pharmacological sciences, 2014•cell.comT 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 …
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 …
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.
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