Local microbleeding facilitates IL-6- and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells.
Local microbleeding facilitates IL-6- and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells.
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DOI：
10.1084/jem.20100900
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发表时间：
2011-01-17
期刊：
影响因子：
--
通讯作者：
Hirano T
中科院分区：
文献类型：
--
作者：
Murakami M;Okuyama Y;Ogura H;Asano S;Arima Y;Tsuruoka M;Harada M;Kanamoto M;Sawa Y;Iwakura Y;Takatsu K;Kamimura D;Hirano T
在CD4+ T细胞缺乏同源抗原识别的情况下，局部微出血诱导Th17细胞的积累和IL-17和il -6依赖性关节炎的发展。CD4+ T细胞的同源抗原识别被认为有助于各种自身免疫性疾病的组织特异性，特别是那些与II类MHC等位基因相关的疾病。然而，我们发现F759小鼠的局部II类mhc依赖性关节炎依赖于在缺乏同源抗原识别的情况下导致活化CD4+ T细胞积累的局部事件。在该模型中，体外极化Th17细胞的转移结合实验性微出血的诱导，导致CCL20的产生，关节内T细胞的积累，以及IL-6的局部产生。疾病的诱导需要通过转移的T细胞产生IL-17A， IL-6和CCL20的表达，以及I型胶原表达细胞中的STAT3信号。我们的数据表明，F759小鼠自身免疫性疾病的发展取决于四个事件：CD4+ T细胞激活，而不考虑抗原特异性，诱导T细胞积累的局部事件，组织中对T细胞源性细胞因子的敏感性增强，以及组织中IL-6信号的激活。这一模型可能解释了为什么活化CD4+ T细胞识别的组织特异性抗原在许多自身免疫性疾病中没有被发现，特别是那些与II类MHC分子相关的疾病。
Local microbleeding induces the accumulation of Th17 cells and the development of IL-17– and IL-6–dependent arthritis in the absence of cognate antigen recognition by CD4+ T cells. Cognate antigen recognition by CD4+ T cells is thought to contribute to the tissue specificity of various autoimmune diseases, particularly those associated with class II MHC alleles. However, we show that localized class II MHC–dependent arthritis in F759 mice depends on local events that result in the accumulation of activated CD4+ T cells in the absence of cognate antigen recognition. In this model, transfer of in vitro polarized Th17 cells combined with the induction of experimental microbleeding resulted in CCL20 production, the accumulation of T cells in the joints, and local production of IL-6. Disease induction required IL-17A production by transferred T cells, IL-6 and CCL20 expression, and STAT3 signaling in type I collagen–expressing cells. Our data suggest a model in which the development of autoimmune disease in F759 mice depends on four events: CD4+ T cell activation regardless of antigen specificity, local events that induce T cell accumulation, enhanced sensitivity to T cell–derived cytokines in the tissue, and activation of IL-6 signaling in the tissue. This model provides a possible explanation for why tissue-specific antigens recognized by activated CD4+ T cells have not been identified in many autoimmune diseases, especially those associated with class II MHC molecules.
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影响因子：
3.2
作者：
Andersson, Ida E.;Batsalova, Tsvetelina;Linusson, Anna
通讯作者：
Linusson, Anna
影响因子：
64.8
作者：
Compagno, Mara;Lim, Wei Keat;Grunn, Adina;Nandula, Subhadra V.;Brahmachary, Manisha;Shen, Qiong;Bertoni, Francesco;Ponzoni, Maurilio;Scandurra, Marta;Califano, Andrea;Bhagat, Govind;Chadburn, Amy;Dalla-Favera, Riccardo;Pasqualucci, Laura
通讯作者：
Pasqualucci, Laura
影响因子：
4.4
作者：
Chapuy-Regaud, S;Sebbag, M;Serre, G
通讯作者：
Serre, G
影响因子：
4.4
作者：
Gudmundsdottir, H;Turka, LA
通讯作者：
Turka, LA
影响因子：
4.4
作者：
Ishihara, K;Sawa, S;Hirano, T
通讯作者：
Hirano, T