MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis
MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis
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DOI：
10.1007/s00535-004-1492-9
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发表时间：
2005-01-01
影响因子：
6.3
通讯作者：
Watanabe, M
中科院分区：
文献类型：
--
作者：
Araki, A;Kanai, T;Watanabe, M
背景资料。肠道共生微生物影响粘膜和系统免疫系统的发展和激活。然而，这些微生物参与结肠炎发展的确切分子机制尚不清楚。方法：研究方法。本研究旨在探讨先天免疫系统在MyD88(-/-)小鼠葡聚糖硫酸钠(DSS)结肠炎模型中的独特作用，因为髓系分化蛋白(MyD88)是通过Toll样受体(TLRs)传递信号的主要适配分子。为此，MyD88(-/-)和野生型(WT)小鼠接受含有1.2%DSS的无菌蒸馏水8天。评估存活率、临床总评分(体重减轻、大便稠度、直肠出血)、结肠长度和组织学评分。免疫组织化学方法检测浸润性固有层单个核细胞表面标志物(F4/80和CD4)的表达。结果。与WT小鼠相比，MyD88(-/-)小鼠对DSS诱导的结肠炎的易感性增加，表现为显著更高的致死率和更高的临床和组织学评分，以及更严重的结肠缩短。免疫组织化学分析显示，与饲喂DSS的WT小鼠相比，饲喂DSS的MyD88(-/-)小鼠炎症粘膜中的F4/80(+)巨噬细胞和CD4(+)T细胞显著增加。结论。这些发现表明，通过MyD88信号，肠道中的先天性免疫系统在结肠炎中起着重要的保护作用。
Background. Gut commensal microbes affect the development and activation of the mucosal and systemic immune systems. However, the exact molecular mechanism of these microbes that is involved in the development of colitis remains unclear. Methods. The present study was conducted to determine the distinct role of the innate immune system in the development of a dextran sulfate sodium (DSS) colitis model in MyD88(-/-) mice, because myeloid differentiation protein (MyD88) is a major adaptor molecule essential for signaling via Toll-like receptors (TLRs). To this end, MyD88(-/-) and wild-type (WT) mice received sterile distilled water containing 1.2% DSS for 8 days. The survival rate, total clinical score (body weight loss, stool consistency, and rectal bleeding), colon length, and histological score were assessed. The expression of surface markers (F4/80 and CD4) on infiltrating lamina propria mononuclear cells was analyzed immunohistochemistrically. Results. MyD88(-/-) mice exhibited increased susceptibility to DSS-induced colitis, as reflected by significantly higher lethality and higher clinical and histological scores, and more severe colonic shortening compared to WT mice. Immunohistochemical analysis revealed a significant increase of both F4/80(+) macrophages and CD4(+) T cells in the inflamed mucosa in DSS-fed MyD88(-/-) mice compared to DSS-fed WT mice. Conclusions. These findings suggest that, via MyD88 signaling, the innate immune system in the gut plays an important protective role in colitis.