IL-23 is essential for T cell–mediated colitis and promotes inflammation via IL-17 and IL-6

J. Clin. Invest. 16: 1310-1316 (2006)

Speaker: 林建達                 Time: 2006/10/11 14:00-15:00

Commentator: 林秋烽 老師       Place: Room 601

Abstract:

Uncontrolled mucosal immunity in the gastrointestinal tract of humans results in chronic inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis. IBD is a group of chronic disorders that causes inflammation or ulceration in the small and large intestines. While ulcerative colitis affects the inner lining of the colon and rectum, Crohn's disease extends into the deeper layers of the intestinal wall. It is a chronic condition and may recur at various times over a lifetime. In early clinical trials as well as in animal models, IL-12 has been implicated as a major mediator of these diseases based on the ability of anti-p40 monoclonal antibody (mAb) treatment to reverse intestinal inflammation. The cytokine IL-23 shares the same p40 subunit with IL-12, and the anti-p40 mAbs used in human and mouse IBD studies neutralized the activities of both IL-12 and IL-23. Furthermore, IL-10–deficient mice spontaneously develop enterocolitis. To determine how IL-23 contributes to intestinal inflammation, the authors studied the disease susceptibility in the absence of either IL-23 or IL-12 in this model, as well as the ability of recombinant IL-23 to exacerbate IBD induced by T cell transfer. The authors showed that in these models, IL-23 is essential for manifestation of chronic intestinal inflammation, whereas IL-12 is not. A critical target of IL-23 is a unique subset of tissue-homing memory T cells, which are specifically activated by IL-23 to produce the proinflammatory mediators IL-17 and IL-6. This pathway may be responsible for chronic intestinal inflammation as well as other chronic autoimmune inflammatory disease.

References:

1.     Braegger, C.P. 1994. Immunopathogenesis of chronic inflammatory bowel disease. Acta Paediatr. Suppl. 83:18–21.

2. Langrish, C.L., et al. 2005. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201:233–240.