IL-23-driven encephalo-tropism and Th17 polarization during CNS-inflammation in vivo
IL-23-driven encephalo-tropism and Th17 polarization during CNS-inflammation in vivo
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DOI：
10.1002/eji.200939305
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发表时间：
2009-07-01
影响因子：
5.4
通讯作者：
Becher, Burkhard
中科院分区：
文献类型：
--
作者：
Gyuelveszi, Gabor;Haak, Stefan;Becher, Burkhard
IL-23而不是IL-12是小鼠自身免疫组织炎症发展所必需的。相反，IL-12和IL-23分别影响Th 1和Th 17细胞的极化。虽然这两种极化的辅助性T细胞群体都可以介导自身免疫性炎症，但它们在EAE发病机制中的冗余表明IL-23对疾病发挥了重要影响，而不依赖于其辅助性T细胞极化能力。为了研究IL-23和IL-12对致脑炎性T细胞在体内的行为的影响，我们产生了BM嵌合小鼠，其中我们可以在EAE期间追踪IL-23或IL-12应答性T辅助细胞的个体群体。我们观察到缺乏IL-12 R β 1（无IL-12和IL-23信号传导）的T细胞不能侵入CNS，也不能获得Th 17表型。相比之下，IL-12信号传导的丧失阻止Th 1极化，但不阻止T细胞进入CNS。IL-12 R结合的丧失似乎不会改变T细胞扩增，但会导致其在次级淋巴器官中的积累。我们发现IL-23允许T细胞侵入靶组织并发挥其效应功能，而IL-12对Th 1分化至关重要，但不影响体内自身反应性T辅助细胞的致病能力。
IL-23 but not IL-12 is essential for the development of autoimmune tissue inflammation in mice. Conversely, IL-12 and IL-23 impact on the polarization of Th1 and Th17 cells, respectively. While both polarized T helper populations can mediate autoimmune inflammation, their redundancy in the pathogenesis of EAE indicates that IL-23 exerts its crucial influence on the disease independent of its T helper polarizing capacity. To study the impact of IL-23 and IL-12 on the behavior of encephalitogenic T cells in Vivo, we generated BM-chimeric mice in which we can trace individual populations of IL-23 or IL-12 responsive T helper cells during EAE. We observed that T cells, which lack IL-12R beta 1 (no IL-12 and IL-23 signaling), fail to invade the CNS and do not acquire a Th17 phenotype. In contrast, loss of IL-12 signaling prevents Th1 polarization but does not prevent T-cell entry into the CNS. The loss of IL-12R engagement does not appear to alter T-cell expansion but leads to their accumulation in secondary lymphoid organs. We found that IL-23 licenses T cells to invade the target tissue and to exert their effector function, whereas IL-12 is critical for Th1 differentiation, but does not influence the pathogenic capacity of auto-reactive T helper cells in vivo.