Immunity
Volume 25, Issue 2, August 2006, Pages 309-318
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Article
Differential Activity of IL-12 and IL-23 in Mucosal and Systemic Innate Immune Pathology

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Summary

The CD40-CD154 pathway is important in the pathogenesis of inflammatory bowel disease. Here we show that injection of an agonistic CD40 mAb to T and B cell-deficient mice was sufficient to induce a pathogenic systemic and intestinal innate inflammatory response that was functionally dependent on tumor necrosis factor-α and interferon-γ as well as interleukin-12 p40 and interleukin-23 p40 secretion. CD40-induced colitis, but not wasting disease or serum proinflammatory cytokine production, depended on interleukin-23 p19 secretion, whereas interleukin-12 p35 secretion controlled wasting disease and serum cytokine production but not mucosal immunopathology. Intestinal inflammation was associated with IL-23 (p19) mRNA-producing intestinal dendritic cells and IL-17A mRNA within the intestine. Our experiments identified IL-23 as an effector cytokine within the innate intestinal immune system. The differential role of IL-23 in local but not systemic inflammation suggests that it may make a more specific target for the treatment of IBD.

CELLIMMUNO
HUMDISEASE

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4

These authors contributed equally to this work.

5

Present address: Children's Hospital, Department of Pediatric Gastroenterology, University Children's Hospital, Oststr. 21-25, 04317 Leipzig, Germany.