Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice.
Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice.
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DOI：
10.4049/jimmunol.1100854
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发表时间：
2011-10-15
期刊：
影响因子：
--
通讯作者：
Verdu EF
中科院分区：
文献类型：
--
作者：
Galipeau HJ;Rulli NE;Jury J;Huang X;Araya R;Murray JA;David CS;Chirdo FG;McCoy KD;Verdu EF
乳糜泻（CD）常在1型糖尿病（T1 D）患者中诊断，T1 D患者可表现出抗组织转氨酶（CD中的自身抗原）的抗体。因此，麦醇溶蛋白，在CD中的触发器，已被认为在T1 D发病机制中具有作用。本研究的目的是调查麦醇溶蛋白是否有助于NOD-DQ 8小鼠的肠病和胰岛炎，NOD-DQ 8小鼠是一种不会自发发展为T1 D的动物模型。麦胶蛋白致敏的NOD-DQ 8小鼠出现中度肠病、上皮内淋巴细胞增多和屏障功能障碍，但未出现胰岛炎。在麦胶蛋白致敏前给予抗CD 25单克隆抗体可诱导CD 25 + Foxp 3 + T细胞部分耗竭，并导致严重的胰岛炎，但不会加重粘膜功能障碍。从发展为胰岛炎的小鼠的胰腺淋巴结分离的CD 4 + T细胞在与麦胶蛋白孵育后显示出增加的增殖和促炎细胞因子，但与BSA孵育后没有。从非致敏对照中分离的CD 4 + T细胞对麦醇溶蛋白或BSA没有反应。总之，麦胶蛋白致敏诱导NOD-DQ 8小鼠中度肠病。然而，胰岛炎的发展需要麦胶蛋白致敏和CD 25 + Foxp 3 + T细胞的部分全身耗竭。这种人源化的小鼠模型提供了一个机制的联系，以解释如何粘膜不耐受的饮食蛋白质可以导致胰岛炎的存在下，部分调节性T细胞的缺陷。
Celiac disease (CD) is frequently diagnosed in patients with type 1 diabetes (T1D), and T1D patients can exhibit Abs against tissue transglutaminase, the auto-antigen in CD. Thus, gliadin, the trigger in CD, has been suggested to have a role in T1D pathogenesis. The objective of this study was to investigate whether gliadin contributes to enteropathy and insulitis in NOD-DQ8 mice, an animal model that does not spontaneously develop T1D. Gliadin-sensitized NOD-DQ8 mice developed moderate enteropathy, intraepithelial lymphocytosis, and barrier dysfunction, but not insulitis. Administration of anti-CD25 mAbs before gliadin-sensitization induced partial depletion of CD25+Foxp3+ T cells and led to severe insulitis, but did not exacerbate mucosal dysfunction. CD4+ T cells isolated from pancreatic lymph nodes of mice that developed insulitis showed increased proliferation and proinflammatory cytokines after incubation with gliadin but not with BSA. CD4+ T cells isolated from nonsensitized controls did not response to gliadin or BSA. In conclusion, gliadin sensitization induced moderate enteropathy in NOD-DQ8 mice. However, insulitis development required gliadin-sensitization and partial systemic depletion of CD25+Foxp3+ T cells. This humanized murine model provides a mechanistic link to explain how the mucosal intolerance to a dietary protein can lead to insulitis in the presence of partial regulatory T cell deficiency.
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影响因子：
13.6
作者：
Borchers, Andrea T.;Uibo, Raivo;Gershwin, M. E.
通讯作者：
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影响因子：
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作者：
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48
作者：
Hadjivassiliou, Marios;Sanders, David S.;Aeschlimann, Daniel
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影响因子：
--
作者：
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通讯作者：
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影响因子：
8.2
作者：
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通讯作者：
Paroni, R.