Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
J Immunol. 2010 Dec 15;185(12):7671-80. doi: 10.4049/jimmunol.1002229. Epub 2010 Nov 10.
We have previously found that CD30 ligand (CD30L; CD153)/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production. In this study, we investigated the role of CD30L in the development of colitis experimentally induced by dextran sulfate sodium (DSS), in which IL-17A is involved in the pathogenesis. CD30L(-/-) mice were resistant to both acute colitis induced by administration of 3 to ∼ 5% DSS and to chronic colitis induced by administration of 1.5% DSS on days 0-5, 10-15, and 20-25 as assessed by weight loss, survival rate, and histopathology. The levels of IFN-γ, IL-17A, and IL-10 were significantly lower but the IL-2 level higher in the lamina propria T lymphocytes of CD30L(-/-) mice than those in lamina propria T lymphocytes of wild-type mice after DSS administration. Soluble murine CD30-Ig fusion protein, which was capable of inhibiting Th17 cell differentiation in vitro, ameliorated both types of DSS-induced colitis in wild-type mice. Modulation of CD30L/CD30 signaling by soluble CD30 could be a novel biological therapy for inflammatory diseases associated with Th17 responses.
我们之前发现，T 细胞与 T 细胞的相互作用所执行的 CD30 配体（CD30L；CD153）/CD30 信号转导在 Th17 细胞分化中起着关键作用，至少部分是通过下调 IL-2 的产生。在这项研究中，我们研究了 CD30L 在葡聚糖硫酸钠（DSS）诱导的实验性结肠炎发展中的作用，其中 IL-17A 参与了发病机制。与野生型小鼠相比，CD30L（-/-）小鼠对 3 至约 5% DSS 诱导的急性结肠炎和 0-5、10-15 和 20-25 天 1.5% DSS 诱导的慢性结肠炎均具有抗性，这通过体重减轻、存活率和组织病理学来评估。与野生型小鼠相比，CD30L（-/-）小鼠的固有层 T 淋巴细胞中 IFN-γ、IL-17A 和 IL-10 的水平显著降低，但 IL-2 的水平升高。可溶性鼠 CD30-Ig 融合蛋白能够体外抑制 Th17 细胞分化，改善野生型小鼠的两种 DSS 诱导的结肠炎。可溶性 CD30 对 CD30L/CD30 信号的调节可能成为与 Th17 反应相关的炎症性疾病的一种新的生物治疗方法。
