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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.

Original publication

DOI

10.1016/j.immuni.2006.05.017

Type

Journal article

Journal

Immunity

Publication Date

08/2006

Volume

25

Pages

309 - 318

Keywords

Animals, Antibodies, CD40 Antigens, Colitis, Immunity, Innate, Immunity, Mucosal, Interleukin-12, Interleukin-23, Interleukin-23 Subunit p19, Interleukins, Mice, Mice, Knockout, Organ Specificity, Spleen, T-Lymphocytes, Wasting Syndrome