Gliadin-primed CD4+CD45RBlowCD25- T cells drive gluten-dependent small intestinal damage after adoptive transfer into lymphopenic mice.
Gliadin-primed CD4+CD45RBlowCD25- T cells drive gluten-dependent small intestinal damage after adoptive transfer into lymphopenic mice.
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DOI：
10.1136/gut.2009.186361
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发表时间：
2009-12
期刊：
影响因子：
24.5
通讯作者：
Schuppan D
中科院分区：
文献类型：
--
作者：
Freitag TL;Rietdijk S;Junker Y;Popov Y;Bhan AK;Kelly CP;Terhorst C;Schuppan D
乳糜泻（cd）是一种常见的小肠炎症性疾病，由麸质反应效应T细胞驱动，由肠道对饮食麸质蛋白的耐受性破坏引起。我们的目的是评估谷蛋白反应效应T细胞的致病作用，并建立一个谷蛋白诱导的肠病模型。CD4+CD25−T细胞组分被过继地转移到淋巴细胞减少的小鼠体内，导致“基线”小肠炎症。Rag1−/−接受麦胶蛋白呈递的CD4+CD45RBlowCD25−T细胞，而不是CD4+CD45RBhigh初始T细胞，与无麸质饮食的受体或对照（卵清蛋白）呈递的T细胞相比，口服谷蛋白刺激的受体体重增加更少，患更严重的十二指肠炎。伴有cd粘膜组织学特征的恶化，十二指肠和周围Th1/Th17细胞极化增加。有趣的是，重新引入无麸质饮食导致体重增加，组织学十二指肠炎的改善，十二指肠IFNγ和IL-17转录物的减少。此外，B细胞胜任的麦胶蛋白呈递T细胞裸受体仅在口服谷蛋白刺激时产生高水平的血清抗麦胶蛋白IgA和IgG1/IgG2c。CD4+ T细胞对谷蛋白的免疫导致淋巴细胞减少小鼠的口服谷蛋白耐受性破坏和小肠病理，类似于人类的cd。该模型将有助于研究cd的发病机制，也可用于测试新的非饮食治疗cd的方法。
Celiac disease (cd) is a common small intestinal inflammatory disorder that results from a breach of intestinal tolerance to dietary gluten proteins, driven by gluten-reactive effector T cells. We aimed to assess the pathogenic role of gluten-reactive effector T cells and to generate a model of gluten-induced enteropathy. CD4+CD25− T cell fractions were adoptively transferred into lymphopenic mice, leading to “baseline” small intestinal inflammation. Rag1−/− recipients of gliadin-presensitized CD4+CD45RBlowCD25− T cells, but not CD4+CD45RBhigh naive T cells, gained less weight and suffered from more severe duodenitis when challenged with oral gluten than recipients on gluten-free diet, or recipients of control (ovalbumin)-presensitized T cells. This was accompanied by deterioration of mucosal histological features characteristic of cd, and increased Th1/Th17 cell polarization in the duodenum and the periphery. Interestingly, reintroduction of a gluten-free diet led to weight gain, improvement of histological duodenitis, and a decrease in duodenal IFNγ and IL-17 transcripts. Moreover, B cell-competent nude recipients of gliadin-presensitized T cells produced high levels of serum anti-gliadin IgA and IgG1/IgG2c only when challenged with oral gluten. CD4+ T cell immunity to gluten leads to a breach of oral gluten tolerance and small intestinal pathology in lymphopenic mice, similar to human cd. This model will be useful for the study of cd pathogenesis, but also for testing novel non-dietary therapies for cd.
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影响因子：
25.7
作者：
Popov, Y;Patsenker, E;Schuppan, D
通讯作者：
Schuppan, D
影响因子：
29.4
作者：
LOFT, DE;MARSH, MN;BAKER, R
通讯作者：
BAKER, R
DOI：
10.1084/jem.186.10.1749
发表时间：
1997-11-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mizoguchi A;Mizoguchi E;Smith RN;Preffer FI;Bhan AK
通讯作者：
Bhan AK
影响因子：
2.6
作者：
Bachmanov, AA;Reed, DR;Tordoff, MG
通讯作者：
Tordoff, MG
DOI：
10.1038/ncpgasthep0582
发表时间：
2006-09-01
期刊：
NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY
影响因子：
--
作者：
Jabri, Bana;Sollid, Ludvig M.
通讯作者：
Sollid, Ludvig M.