Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology
Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology
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DOI：
10.1016/j.immuni.2006.05.017
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发表时间：
2006-08-01
期刊：
影响因子：
32.4
通讯作者：
Powrie, Fiona
中科院分区：
文献类型：
--
作者：
Uhlig, Holm H.;McKenzie, Brent S.;Powrie, Fiona
CD40-CD154通路在炎症性肠病的发病机制中起重要作用。在这里，我们表明，向T和B细胞缺陷小鼠注射激动型CD40单抗足以诱导致病性全身和肠道先天炎症反应，这种反应在功能上依赖于肿瘤坏死因子-α和干扰素-γ以及IL-12p40和IL-23p40的分泌。CD40诱导的结肠炎依赖于IL-23p19的分泌，而不是衰竭性疾病或血清促炎细胞因子的产生，而IL-12p35的分泌控制衰减性疾病和血清细胞因子的产生，而不是粘膜免疫病理。肠道炎症与肠内产生IL-23(P19)mRNA的肠树突状细胞和IL-17A mRNA有关。我们的实验证实IL-23是肠道固有免疫系统中的一种效应细胞因子。IL-23在局部而不是全身炎症中的不同作用表明，它可能成为治疗IBD的更特异的靶点。
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.