CD30 Ligand Is a Target for a Novel Biological Therapy against Colitis Associated with Th17 Responses
CD30 Ligand Is a Target for a Novel Biological Therapy against Colitis Associated with Th17 Responses
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DOI：
10.4049/jimmunol.1002229
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发表时间：
2010-12-15
影响因子：
4.4
通讯作者：
Yoshikai, Yasunobu
中科院分区：
文献类型：
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作者：
Sun, Xun;Yamada, Hisakata;Yoshikai, Yasunobu
我们之前已经发现CD30配体(CD30L; CD153)/CD30信号通过T-T细胞相互作用在Th17细胞分化中起关键作用，至少部分是通过下调IL-2的产生。在本研究中，我们研究了CD30L在葡聚糖硫酸钠（DSS）实验性诱导的结肠炎发展中的作用，其中IL-17A参与了其发病机制。通过体重减轻、存活率和组织病理学评估，CD30L（-/-）小鼠在0-5、10-15和20-25天对3 - 5% DSS诱导的急性结肠炎和1.5% DSS诱导的慢性结肠炎均有抗性。DSS给药后，CD30L（-/-）小鼠固有层T淋巴细胞中ifn - γ、IL-17A、IL-10水平明显低于野生型小鼠，IL-2水平明显高于野生型小鼠。可溶性小鼠CD30-Ig融合蛋白能够在体外抑制Th17细胞分化，改善了野生型小鼠dss诱导的两种结肠炎。通过可溶性CD30调节CD30L/CD30信号可能是一种新的生物疗法，用于治疗与Th17反应相关的炎症性疾病。免疫学杂志，2010,18(5):771 - 778。
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 similar 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-gamma, 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. The Journal of Immunology, 2010, 185: 7671-7680.