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首页> 外文期刊>Inflammatory bowel diseases >Alterations in myeloid dendritic cell innate immune responses in the Galphai2-deficient mouse model of colitis.
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Alterations in myeloid dendritic cell innate immune responses in the Galphai2-deficient mouse model of colitis.

机译：骨髓内突细胞的改变在Galphai2缺陷的结肠炎小鼠模型中的粘蛋白树突细胞先天免疫应答。

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BACKGROUND: The G protein alpha subunit type-2 (Galpha(i)2)-deficient mouse develops inflammatory bowel disease (IBD) with increased severity in mice on a 129SvEv (129) background compared to the C57BL/6 (B6) background. Since dendritic cells (DCs) are key cells of innate immunity, we determined whether Galpha(i)2(-/-) DCs have functional defects, influenced by strain background, that predispose to IBD. METHODS: By breeding these strains to homozygosity for the first time, it became possible to study innate immunity in this animal model with more precision than ever before. Immature DCs were generated using bone marrow monoblasts cultured in the presence of GM-CSF (BMDCs), DC subsets sorted and responses to TLR9 activation were assayed. RESULTS: In contrast to Galpha(i)2(-/-) B6, Galpha(i)2(-/-) 129 mice display accelerated onset and increased severity of colitis, abnormal mucosal DC distribution, accompanied by preponderance for Th1 and Th17-associated gut cytokine expression. TLR9 activation of BMDCsinduces sustained p38 MAPK activation and greater Th1- and Th17-type cytokine secretion in both strains of Galpha(i)2-deficient compared to wildtype BMDCs. However, only B6 Galpha(i)2(-/-) BMDCs concomitantly produces IL-10 while Galpha(i)2(-/-) 129 BMDCs do not. CONCLUSIONS: Loss of Galpha(i)2 promotes a Th1/Th17 phenotype and relative IL-10 insufficiency in Galpha(i)2(-/-) 129 BMDCs may account for the striking difference in disease.
机译：背景：G蛋白α亚单位型-2（Galpha（I）2） - 与C57BL / 6（B6）背景相比，在129SVEV（129）背景下，在129SVEV（129）背景下，对小鼠的严重程度增加了炎症性肠病（IBD）。由于树突细胞（DCS）是先天免疫的关键细胞，因此Chatpha（I）2（ - / - ）DC的功能缺陷是由应变背景的影响，从而达到IBD。方法：通过首次将这些菌株育种到纯合子，它可以以比以前更精确地研究这种动物模型中的先天免疫力。使用在GM-CSF（BMDCS）存在下培养的骨髓单卵细胞产生未成熟的DC，测定分选和对TLR9活化的反应进行分类的DC子集。结果：与Galpha（I）2（ - / - ）B6，Galpha（I）2（ - / - ）129小鼠显示加速发作和结肠炎的严重程度，异常粘膜DC分布，伴随着Th1和Th17的优势 - 化的肠道细胞因子表达。与野生型BMDC相比，TLR9对BMDCSINDUCTS的激活持续的P38 MAPK激活和更高的GALPHA（I）株的细胞因子分泌。然而，只有B6 Galpha（I）2（ - / - ）BMDC伴随着Galpha（i）2（ - / - ）129 BMDC的同时产生IL-10。结论：Galpha（I）2的丧失促进了Galpha（I）2（ - / - ）129 BMDCs的Th1 / Th17表型和相对IL-10不足，可能会占疾病的突出差异。

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