Th17 Cells and Inflammatory Bowel Disease

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Annu Rev Med. 2008 Oct 31. [Epub ahead of print]

IL-23 and Autoimmunity: New Insights into the Pathogenesis of

Inflammatory Bowel Disease.

Abraham C, Cho JH

Section of Digestive Diseases, Departments of Medicine, Yale

University,New Haven, Connecticut 06520; email:

clara.abraham@....

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 Treg subsets. 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. PMID: 18976050.