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

D Yen, J Cheung, H Scheerens… - The Journal of …, 2006 - Am Soc Clin Investig
D Yen, J Cheung, H Scheerens, F Poulet, T McClanahan, B McKenzie, MA Kleinschek…
The Journal of clinical investigation, 2006Am Soc Clin Investig
Uncontrolled mucosal immunity in the gastrointestinal tract of humans results in chronic
inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis. 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 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 …
Uncontrolled mucosal immunity in the gastrointestinal tract of humans results in chronic inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis. 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 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. IL-10–deficient mice spontaneously develop enterocolitis. To determine how IL-23 contributes to intestinal inflammation, we 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. Our study shows 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 diseases.
The Journal of Clinical Investigation