Heligmosomoides polygyrus abrogates antigen-specific gut injury in a murine model of inflammatory bowel disease.
Heligmosomoides polygyrus abrogates antigen-specific gut injury in a murine model of inflammatory bowel disease.
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DOI：
10.1002/ibd.22858
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发表时间：
2012-08
影响因子：
4.9
通讯作者：
Weinstock, Joel
中科院分区：
文献类型：
--
作者：
Leung, John;Hang, Long;Blum, Arthur;Setiawan, Tommy;Stoyanoff, Korynn;Weinstock, Joel
发展中国家炎症性肠病（IBD）的发病率较低，这可能是由于蠕虫感染和肠道植物群和动物群的其他改变的高患病率。蠕虫感染可预防各种IBD小鼠模型中的结肠炎。IBD可由对管腔抗原的异常免疫应答驱动。因此，我们开发了一种IBD小鼠模型，其中肠道损伤由特异性抗原诱导，以更好地模拟IBD疾病过程，并确定蠕虫感染是否可以消除口服抗原诱导的肠道损伤。该模型的特点是由喂食卵白蛋白引发的泛小肠结肠炎。肠道炎症是抗原特异性的，产生IL-17和IFN-γ，但不产生IL-4。这种疾病的完全表达需要具有制造IL-10的缺陷能力的T细胞和用无损伤的低剂量非甾体抗炎药治疗。暴露于H。多脑回消除了这种抗原诱导的肠损伤。H.多脑回定殖诱导Foxp 3 + T细胞和粘膜产生来自非T细胞的IL-10。固有层单个核细胞来自H.多脑回感染的小鼠组成性地释放较少的IL-17和IFN-γ，并且当用OVA或抗CD 3/CD 28 mAb刺激时。总之，我们建立了一个以抗原特异性小肠结肠炎为特征的小鼠IBD模型，并首次证明了抗原诱导的肠道炎症可以被H.多脑回感染保护作用与抑制IL-17和IFN-γ的产生、诱导Foxp 3 + T细胞和升高非T细胞来源的IL-10的分泌有关，所有这些都可能是保护过程的一部分。
Developing countries have a low incidence of inflammatory bowel disease (IBD), perhaps prevented by the high prevalence of helminth infections and other alterations in intestinal flora and fauna. Helminth infections prevent colitis in various murine models of IBD. IBD may be driven by an aberrant immune response to luminal antigen(s). We therefore developed a murine model of IBD in which gut injury was induced by a specific antigen to better simulate the IBD disease process and to determine if helminth infections could abolish gut injury induced by an orally administered antigen. The model features pan-enterocolitis triggered by feeding ovalbumin. The intestinal inflammation is antigen-specific and generates IL-17 and IFN-γ, but not IL-4. Full expression of the disease required T cells with defective capacity to make IL-10 and treatment with a non-injurious, low dose of a non-steroidal anti-inflammatory drug. Exposure to H. polygyrus abrogated this antigen-induced gut injury. H. polygyrus colonization induced Foxp3+ Tregs and mucosal production of IL-10 from non-T cells. Lamina propria mononuclear cells from H. polygyrus infected mice released less IL-17 and IFN-γ constitutively and when stimulated with OVA or anti-CD3/CD28 mAbs. In conclusion, we developed a murine IBD model featuring antigen-specific enterocolitis and demonstrated for the first time that gut inflammation induced by an antigen could be abrogated by H. polygyrus infection. Protection was associated with suppressed IL-17 and IFN-γ production, induction of Foxp3+ Tregs and elevated secretion of non-T cells derived IL-10, all of which could be part of the protective processes.
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影响因子：
3.1
作者：
Rausch, Sebastian;Huehn, Jochen;Hartmann, Susanne
通讯作者：
Hartmann, Susanne
影响因子：
5.4
作者：
Finney, Constance A M;Taylor, Matthew D;Wilson, Mark S;Maizels, Rick M
通讯作者：
Maizels, Rick M
影响因子：
3.1
作者：
Saunders, Karin A.;Raine, Tim;Lawrence, Catherine E.
通讯作者：
Lawrence, Catherine E.
DOI：
10.4049/jimmunol.181.4.2414
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Elliott DE;Metwali A;Leung J;Setiawan T;Blum AM;Ince MN;Bazzone LE;Stadecker MJ;Urban JF Jr;Weinstock JV
通讯作者：
Weinstock JV
影响因子：
5.4
作者：
Elliott, DE;Setiawan, T;Weinstock, JV
通讯作者：
Weinstock, JV