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口服耐受在葡聚糖硫酸钠诱导结肠炎中的治疗作用:通过 Th1-Th2 平衡和 γδ T 细胞。

The therapeutic role of oral tolerance in dextran sulfate sodium-induced colitis via Th1-Th2 balance and γδ T cells.

机构信息

Department of Gastroenterology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.

出版信息

J Dig Dis. 2013 Oct;14(10):543-51. doi: 10.1111/1751-2980.12068.

Abstract

OBJECTIVE

To evaluate the state of oral tolerance and its therapeutic role in mice with dextran sulfate sodium (DSS)-induced colitis.

METHODS

Delayed-type hypersensitivity (DTH) was determined 7 and 14 days after DSS-induced colitis and control mice. Disease activity index (DAI) score and colonic histopathological score were measured 7 days after colonic extracted protein (CEP) or bovine serum albumin (BSA) (control) was administrated, with the evaluation of Th1-Th2 balance in the spleen, Peyer's patch and γδ T cells in intraepithelial lymphocytes and lamina proper lymphocytes in the intestine.

RESULTS

After fed with 250 μg ovalbumin oral tolerance was induced in 7 days in both DSS-induced colitis and control mice, while oral tolerance persisted in the control mice but vanished in DSS-induced colitis 14 days after ovalbumin challenge. DAI and colonic histopathological scores were decreased significantly after the ingestion of CEP (controlled by BSA) in DSS-induced colitis with significant reduction of Th1 and the ratio of Th1 to Th2 in Peyer's patch as well as the γδ T cells in lamina proper lymphocytes in the intestine. No significant difference in Th1-Th2 balance in the spleen and γδ T cells in intraepithelial lymphocytes in the intestine were observed.

CONCLUSIONS

There is a defect in oral tolerance at day 7 in DSS-induced colitis. If taken orally, CEP may have a protective role in DSS-induced colitis, which may be related to the deflection from Th1 to Th2 in Peyer's patch and the reduction of γδ T cells in lamina proper lymphocytes in the intestine.

摘要

目的

评估葡聚糖硫酸钠(DSS)诱导结肠炎小鼠的口服耐受状态及其治疗作用。

方法

在 DSS 诱导结肠炎后 7 天和 14 天,测定迟发型超敏反应(DTH)和对照小鼠。在给予结肠提取蛋白(CEP)或牛血清白蛋白(BSA)(对照)后 7 天,测定疾病活动指数(DAI)评分和结肠组织病理学评分,并评估脾、派尔集合淋巴结和上皮内淋巴细胞中的 γδ T 细胞以及固有层淋巴细胞中的 Th1-Th2 平衡。

结果

在给予 250μg 卵清蛋白后,7 天内 DSS 诱导结肠炎和对照小鼠均诱导口服耐受,但在卵清蛋白挑战后 14 天,对照小鼠的口服耐受持续存在,而 DSS 诱导结肠炎小鼠的口服耐受消失。在 DSS 诱导结肠炎小鼠中,口服 CEP(以 BSA 为对照)可显著降低 DAI 和结肠组织病理学评分,同时显著降低派尔集合淋巴结中的 Th1 和 Th1/Th2 比值以及固有层淋巴细胞中的 γδ T 细胞。脾和肠上皮内淋巴细胞中的 Th1-Th2 平衡无显著差异。

结论

DSS 诱导结肠炎在第 7 天存在口服耐受缺陷。如果口服给予 CEP,可能对 DSS 诱导结肠炎具有保护作用,这可能与派尔集合淋巴结中 Th1 向 Th2 的偏向以及固有层淋巴细胞中 γδ T 细胞的减少有关。

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