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

First Author  Uhlig HH Year  2006
Journal  Immunity Volume  25
Issue  2 Pages  309-18
PubMed ID  16919486 Mgi Jnum  J:113470
Mgi Id  MGI:3686815 Doi  10.1016/j.immuni.2006.05.017
Citation  Uhlig HH, et al. (2006) Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25(2):309-18
abstractText  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.
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