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 cel...

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Bibliographic Details
Published in:Annual review of medicine 2009-01, Vol.60 (1), p.97-110
Main Authors: Abraham, Clara, Cho, Judy H
Format: Article
Language:English
Subjects:
Arrhythmias, Cardiac - immunology
Autoimmunity
Crohn's disease
Cytokines
Gene expression
Genomics
Homeostasis
Humans
Immune system
Inflammatory bowel disease
Inflammatory Bowel Diseases - drug therapy
Inflammatory Bowel Diseases - genetics
Inflammatory Bowel Diseases - immunology
Interleukin-23 - genetics
Interleukin-23 - immunology
T cell receptors
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Summary: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.
ISSN:0066-4219
1545-326X
DOI:10.1146/annurev.med.60.051407.123757