IL-23 and autoimmunity: new insights into the pathogenesis of inflammatory bowel disease.

The intestinal immune system has the challenge of maintaining both a state of tolerance toward intestinal antigens and the ability to combat pathogens. This balance is partially achieved by reciprocal regulation of proinflammatory, effector CD4(+) T cells and tolerizing, suppressive regulatory T cells. Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis (UC). Genome-wide association studies have linked CD to a number of IL-23 pathway genes, notably IL23R (interleukin 23 receptor). Similar associations in IL-23 pathway genes have been observed in UC. IL23R is a key differentiation feature of CD4(+) Th17 cells, effector cells that are critical in mediating antimicrobial defenses. However, IL-23 and Th17 cell dysregulation can lead to end-organ inflammation. The differentiation of inflammatory Th17 cells and suppressive CD4(+) Treg subsets is reciprocally regulated by relative concentrations of TGFbeta, with the concomitant presence of proinflammatory cytokines favoring Th17 differentiation. The identification of IL-23 pathway and Th17 expressed genes in IBD pathogenesis highlights the importance of the proper regulation of the IL-23/Th17 pathway in maintaining intestinal immune homeostasis.

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