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

Journal article

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.

Authors: Uhlig, H; McKenzie, B; Hue, S; Thompson, C; Joyce-Shaikh, B

• Publication status: Published
• Journal: Immunity
• Volume: 25
• Issue: 2
• Pages: 309-318
• Publication date: 2006-08-01
• DOI: 10.1016/j.immuni.2006.05.017
• EISSN: 1097-4180
• ISSN: 1074-7613
• Language: English
• Keywords: T-Lymphocytes; Interleukin-23; Organ Specificity; Spleen; Colitis; Mice, Knockout; Animals; Immunity, Innate; Interleukin-23 Subunit p19; Mice; Antigens, CD40; Wasting Syndrome; Interleukins; Antibodies; Immunity, Mucosal; Interleukin-12