Exposure to schistosome eggs protects mice from TNBS-induced colitis

Exposure to schistosome eggs protects mice from TNBS-induced colitis
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DOI:
10.1152/ajpgi.00049.2002
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发表时间:
2003-03-01
影响因子:
4.5
通讯作者:
Weinstock, JV
Weinstock, JV
中科院分区:
医学2区
文献类型:
--
作者:
Elliott, DE;Li, J;Weinstock, JV

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克罗恩病是由辅助性T细胞(Th)1型粘膜炎症失调引起的。克罗恩病在热带国家很少见,但在温带气候的发达国家很流行,1940年后发病率上升。相比之下,接触蠕虫寄生虫在热带国家很常见,但在发达国家很少见。蠕虫寄生虫在宿主中诱导免疫调节性T细胞应答。我们推测,蠕虫引起的免疫调节反应可能会减弱过度的Th 1型炎症。为了验证这一假设,将小鼠暴露于曼氏血吸虫卵,然后用三硝基苯磺酸(TNBS)直肠激发以诱导结肠炎。血吸虫卵暴露减弱TNBS结肠炎并保护小鼠免受致命炎症。血吸虫卵暴露减少了IFN-γ,增强了TNBS处理小鼠的α CD 3刺激的脾和肠系膜淋巴结细胞的IL-4产生。血吸虫卵暴露减少结肠IFN-γ,但增加IL-10 mRNA的表达在TNBS治疗的小鼠。完整的信号转导子和转录激活子6是减轻结肠炎所必需的。接触蠕虫可以减少小鼠结肠炎症。
Crohn's disease results from dysregulated T helper (Th) 1-type mucosal inflammation. Crohn's disease is rare in tropical countries but prevalent in developed countries with temperate climates, in which its incidence rose after 1940. In contrast, exposure to helminthic parasites is common in tropical countries but is rare in developed countries. Helminthic parasites induce immunomodulatory T cell responses in the host. We hypothesize that immunomodulatory responses due to helminths may attenuate excessive Th1-type inflammation. To test that hypothesis, mice were exposed to eggs of the helminth Schistosoma mansoni and then challenged rectally with trinitrobenzesulfonic acid (TNBS) to induce colitis. Schistosome egg exposure attenuated TNBS colitis and protected mice from lethal inflammation. Schistosome egg exposure diminished IFN-gamma and enhanced IL-4 production from alphaCD3-stimulated spleen and mesenteric lymph node cells of TNBS-treated mice. Schistosome egg exposure decreased colonic IFN-gamma but increased IL-10 mRNA expression in TNBS-treated mice. Intact signal transducer and activator of transcription 6 was required for attenuation of colitis. Exposure to helminths can decrease murine colonic inflammation.