Interleukin-23/Th17 pathways and inflammatory bowel disease

Abstract

The IL-23/Th17 pathway has recently been identified to play a critical role in a number of chronic inflammatory diseases including inflammatory bowel disease (IBD). The identification in IBD patients of associations in IL23R and regions that include other genes in the IL-23/Th17 pathway has highlighted the importance of proper IL-23/Th17 pathway regulation in intestinal immune homeostasis. IL-23 plays a role in CD4+ Th17 lineage cells, characterized by IL-17 secretion and the expression of the transcription factor retinoic acid-related orphan receptor (ROR)gamma tau, and in other immune and nonimmune cells. The balance between effector T cell subsets, such as Th17 cells, and CD4+ T regulatory subsets is finely regulated; dysregulation of this balance can lead to inflammation and autoimmunity. As such, the IL-23/Th17 pathway contributes to immune responses that play a role in defenses to microbial infection, as well as in the intestinal inflammation observed in both animal models of colitis and human IBD.