Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis
Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis
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DOI：
10.4049/jimmunol.177.5.2760
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发表时间：
2006-09-01
影响因子：
4.4
通讯作者：
Neurath, Markus F.
中科院分区：
文献类型：
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作者：
Becker, Christoph;Dornhoff, Heike;Neurath, Markus F.
虽然IL-12和IL-23共享共同的p40亚基，但IL-23而不是IL-12似乎驱动实验性自身免疫性脑脊髓炎和关节炎的发病机制，因为IL-23/p19敲除小鼠免受疾病的影响。相反，我们在这项研究中描述了新创建的IL-23 p19缺陷的LacZ敲入小鼠对实验性T细胞介导的TNBS结肠炎的发展高度敏感，并且通过内窥镜和组织学标准显示出比野生型小鼠更严重的结肠炎。随后的研究表明，来自p19缺陷小鼠的树突状细胞产生升高水平的IL-12，并且IL-23在TLR连接后下调IL-12表达。最后，IL-23缺陷小鼠体内IL-12 p40的阻断使小鼠免于致死性结肠炎。总之，我们的数据确定了IL-23对IL-12表达的交叉调节是T细胞依赖性结肠炎起始期间的新的关键调节途径。
Although IL-12 and IL-23 share the common p40 subunit, IL-23, rather than IL-12, seems to drive the pathogenesis of experimental autoimmune encephalomyelitis and arthritis, because IL-23/p19 knockout mice are protected from disease. In contrast, we describe in this study that newly created LacZ knockin mice deficient for IL-23 p19 were highly susceptible for the development of experimental T cell-mediated TNBS colitis and showed even more severe colitis than wild-type mice by endoscopic and histologic criteria. Subsequent studies revealed that dendritic cells from p19-deficient mice produce elevated levels of IL-12, and that IL-23 down-regulates IL-12 expression upon TLR ligation. Finally, in vivo blockade of IL-12p40 in IL-23-deficient mice rescued mice from lethal colitis. Taken together, our data identify cross-regulation of IL-12 expression by IL-23 as novel key regulatory pathway during initiation of T cell dependent colitis.