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Immunity. 2006 Aug;25(2):309-18.

Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology.

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1
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, OX1 3RE Oxford, UK.

Abstract

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-alpha and interferon-gamma 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.

PMID:
16919486
DOI:
10.1016/j.immuni.2006.05.017
[Indexed for MEDLINE]
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