Induction and Activation of Adaptive Immune Populations During Acute and Chronic Phases of a Murine Model of Experimental Colitis
Induction and Activation of Adaptive Immune Populations During Acute and Chronic Phases of a Murine Model of Experimental Colitis
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DOI：
10.1007/s10620-010-1240-3
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发表时间：
2011-01-01
影响因子：
3.1
通讯作者：
Melgar, Silvia
中科院分区：
文献类型：
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作者：
Hall, Lindsay J.;Faivre, Emilie;Melgar, Silvia
背景 右旋糖酐硫酸钠 (DSS) 通常用于诱导啮齿动物肠道炎症。尽管它作为检查 IBD 发病机制的模型系统仍然很重要，但粘膜和全身免疫反应尚未得到全面记录。目的本研究的目的是剖析与急性和慢性 DSS 诱导的结肠炎相关的两个免疫区室的功能和表型变化。方法 C57BL/6 小鼠暴露于 3% DSS 6 天，然后喝 20 天水，并在这两个过程中收获器官（脾脏、MLN 和结肠）。结果 早在 DSS 后 1 天，就注意到所有检查的先天细胞群的百分比、分布和激活状态发生了显着变化。这些显着差异在整个急性期（第 5-12 天）的全身和粘膜淋巴组织中持续存在。值得注意的是，在急性期和慢性期后期，T 细胞和 B 细胞在结肠中积累。相比之下，在慢性炎症小鼠的脾脏中，T 细胞和 B 细胞显着减少，而中性粒细胞、巨噬细胞以及 IL-6 和 IL-17 阳性细胞增加。结论我们的数据为 DSS 给药诱导的粘膜和全身免疫反应提供了重要的见解。值得注意的是，我们表明在急性和慢性结肠炎期间都会诱导适应性免疫反应。这将有助于更明智和更复杂地使用该模型，以研究肠道炎症的基本机制和评估 IBD 的潜在新治疗药物。
Background Dextran sodium sulphate (DSS) is commonly used to induce intestinal inflammation in rodents. Despite its continuing importance as a model system for examining IBD pathogenesis, the mucosal and systemic immune responses have not been comprehensively documented.Aims The purpose of this study was to dissect functional and phenotypic changes in both immune compartments associated with acute and chronic DSS-induced colitis.Methods C57BL/6 mice were exposed to 3% DSS for 6 days followed by 20 days of water, and organs (spleens, MLN and colons) were harvested during both acute and chronic phases of colitis to examine innate and adaptive cell populations.Results As early as 1 day post DSS, significant changes in the percentage, distribution and activation status of all innate cell populations examined were noted. These striking differences continued in systemic and mucosal lymphoid tissues throughout the acute phase (days 5-12). Significantly, during the late acute and chronic phases T and B cells accumulated in the colon. In contrast, in the spleens of chronically inflamed mice T and B cells were significantly decreased whereas neutrophils, macrophages, and IL-6 and IL-17 positive cells were increased.Conclusions Our data provides important insights into the mucosal and systemic immune responses induced by DSS administration. Notably, we show that adaptive immune responses are induced during both acute and chronic colitis. This will facilitate a more informed and sophisticated use of this model both for investigating basic mechanisms of intestinal inflammation and for the evaluation of potential new therapeutic agents for IBD.