A critical role of CD30 ligand/CD30 in controlling inflammatory bowel diseases in mice
A critical role of CD30 ligand/CD30 in controlling inflammatory bowel diseases in mice
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DOI：
10.1053/j.gastro.2007.11.004
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发表时间：
2008-02-01
期刊：
影响因子：
29.4
通讯作者：
Yoshikai, Yasunobu
中科院分区：
文献类型：
--
作者：
Sun, Xun;Somada, Shinichi;Yoshikai, Yasunobu
背景与目的：CD30配体(CD30L)是一种全长40kodalton的II型膜相关糖蛋白，属于肿瘤坏死因子家族。炎症性肠病患者血清可溶性CD30水平升高，提示CD30L/CD30信号通路参与了炎症性肠病的发病过程。在本研究中，我们研究了CD30L在恶唑酮(OXA)和三硝基苯磺酸(TNBS)诱导的CD30L基因敲除(KO)小鼠结肠炎中的作用。方法：分别用OXA和TNBS诱导BALB/c和C57BL/6背景的CD30LKO小鼠结肠炎，并观察其临床表现。用酶联免疫吸附试验检测结肠固有层T细胞产生细胞因子的情况。在OXA或TNBS诱导的小鼠结肠炎模型中接种抗IL-4单抗或激动型抗CD30单抗。结果：CD30LKO小鼠对OXA诱导的结肠炎敏感，对TNBS诱导的急性结肠炎耐受。经OXA或TNBS处理的CD30LKO小鼠LP T细胞中IL-4、IL-13等辅助性T细胞2型细胞因子水平显著高于野生型小鼠，而干扰素-γ水平低于野生型小鼠。体内注射激动型抗CD30单抗可减轻OXA诱导的小鼠结肠炎，但加重TNBS诱导的CD30LKO小鼠结肠炎。结论：CD30L/CD30信号通路参与了OXA和TNBS诱导的结肠炎的发生发展。单抗对CD30L/CD30信号的调节可能成为治疗IBD的一种新的生物治疗方法。
Background & Aims: A CD30-ligand (CD30L) is a 40-kilodalton, type II membrane-associated glycoprotein belonging to the tumor necrosis factor family. Serum levels of soluble CD30 increased in inflammatory bowel diseases (IBD), suggesting that CD30L/CD30 signaling is involved in the pathogenesis of IBD. In this study, we investigated the role of CD30L in oxazolone (OXA)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis in CD30L knockout (KO) mice. Methods: Colitis was induced by OXA or TNBS in CD30LKO mice with BALB/c or C57BL/6 background, respectively, and diverse clinical signs of the disease were evaluated. Cytokine production from lamina propria T cells of the colon was assessed by enzyme-linked immunosorbent assay. Anti-interleukin (IL)-4 monoclonal antibody (mAb) or agonistic anti-CD30 mAb was inoculated in mice with colitis induced by OXA or TNBS. Results: CD30LKO mice were susceptible to OXA-induced colitis but resistant to TNBS-induced acute colitis. The levels of T helper cell 2 type cytokines such as IL-4 and IL-13 in the LP T cells were significantly higher, but the levels of interferon gamma were lower in OXA- or TNBS-treated CD30LKO mice than in wild-type mice. In vivo administration of agonistic anti-CD30 mAb ameliorated OXA-induced colitis but aggravated TNBS-induced colitis in CD30LKO mice. Conclusions: These results suggest that CD30L/CD30 signaling is involved in development of both OXA- and TNBS-induced colitis. Modulation of CD30L/CD30 signaling by mAb could be a novel biologic therapy for IBD.