IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice
IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice
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DOI：
10.1172/jci35997
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发表时间：
2009-01-01
影响因子：
15.9
通讯作者：
Waisman, Ari
中科院分区：
文献类型：
--
作者：
Haak, Stefan;Croxford, Andrew L.;Waisman, Ari
Th17细胞与自身免疫性致病性的明确关联暗示Th17细胞因子是慢性自身免疫性疾病（如EAE）的关键介质。为了研究IL-17A对中枢神经系统炎症的影响，我们制造了转基因小鼠，在cre介导重组后，IL-17A可以高水平表达。虽然普遍存在的IL-17A过表达导致皮肤炎症和粒细胞减少，但T细胞特异性IL-17A过表达对小鼠的发育和健康没有明显影响。在EAE的背景下，无论是T细胞驱动的IL-17A过表达，还是IL-17A的完全缺失，对临床疾病的发展都没有重大影响。由于IL-17F可能能够弥补IL-17A的损失，我们也产生了IL-17F缺陷小鼠。该菌株对EAE完全敏感，并且在疾病期间表现出不变的自身反应性T细胞的出现和扩增。为了消除任何一种细胞因子的潜在代偿作用，我们用IL-17A特异性的拮抗单克隆抗体治疗il - 17f缺陷小鼠，再次发现对疾病发展只有很小的有益影响。因此，我们得出结论，IL-17A和IL-17F虽然在致脑性T细胞群中显著表达，但可能对自身免疫性中枢神经系统疾病的发展只起到很小的作用。
The clear association of Th17 cells with autoimmune pathogenicity implicates Th17 cytokines as critical mediators of chronic autoimmune diseases such as EAE. To study the impact of IL-17A on CNS inflammation, we generated transgenic mice in which high levels of expression of IL-17A could be initiated after Cre-mediated recombination. Although ubiquitous overexpression of IL-17A led to skin inflammation and granulocytosis, T cell-specific IL-17A overexpression did not have a perceptible impact on the development and health of the mice. In the context of EAE, neither the T cell-driven overexpression of IL-17A nor its complete loss had a major impact on the development of clinical disease. Since IL-17F may be able to compensate for the loss of IL-17A, we also generated IL-17F-deficient mice. This strain was fully susceptible to EAE and displayed unaltered emergence and expansion of autoreactive T cells during disease. To eliminate potential compensatory effects of either cytokine, we treated IL-17F-deficient mice with antagonistic monoclonal antibodies specific for IL-17A and found again only a minimal beneficial impact on disease development. We conclude therefore that both IL-17A and IL-17F, while prominently expressed by an encephalitogenic T cell population, may only marginally contribute to the development of autoimmune CNS disease.