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AR:疾病易感性或与遗传背景对肠道菌群的影响有关

Arthritis and Rheumatology

2017-12-29Article

6.918

影响因子

原标题:实验性脊柱关节炎中HLA-B27对肠道菌群的影响暗示一种失调的生态模型

① HLA-B27阳性的人易得强直性脊柱炎,在大鼠中转入HLA-B27可诱发脊柱关节炎;② 分析3种遗传背景的HLA-B27转基因鼠的炎症状况、基因表达和肠道菌群;③ Lewis和Fischer鼠均有肠道炎症且免疫失调情况相似,这由结肠和盲肠IL-23/IL-17、IFN等细胞因子和通路激活导致,而DA大鼠中细胞因子失调低水平且无炎症;④ 在不同遗传背景下,HLA-B27对菌群的影响显著不同,Lewis和Fisher大鼠有所重叠,DA大鼠则缺乏促进CD4+Th17 T细胞发育的分节丝状细菌。

脊柱关节炎遗传背景免疫失调细胞因子

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2018-01-10 10:39女巫推荐

Title:
Effects of HLA-B27 on Gut Microbiota in Experimental Spondyloarthritis Implicate an Ecological Model of Dysbiosis

DOI:
10.1002/art.40405

Abstract & Authors:展开

Abstract:
We investigated whether HLA-B27-mediated experimental spondyloarthritis (SpA) is associated with a common gut microbial signature to identify potential drivers of pathogenesis. Effects of HLA-B27 on three genetic backgrounds, Dark Agouti (DA), Lewis, and Fischer were compared, using wild-type littermates and HLA-B7 transgenic Lewis rats as controls. At 2, 3-4, and 6-8 months of age, cecal and colonic tissue or contents were analyzed by histology for inflammation, RNA-Seq for gene expression differences, and 16S rRNA gene sequencing for microbiota differences. HLA-B27 transgenic Lewis and Fischer rats develop gut inflammation, while DA rats are resistant to effects of HLA-B27, and HLA-B7 transgenic rats remain unaffected. Immune dysregulation in affected Lewis and Fischer rats is similar and dominated by activation of IL-23/IL-17, IFN, TNF, and IL-1 cytokines and pathways in colon and cecum, while DA rats exhibit low-level cytokine dysregulation without inflammation. Gut microbial changes in HLA-B27 transgenic rats are strikingly divergent on the three different backgrounds, including different patterns of dysbiosis in HLA-B27 transgenic Lewis and Fischer strains with some overlap. Interestingly, DA rats lack segmented filamentous bacteria (SFB) that promote CD4+ Th17 T-cell development, which may explain their resistance to disease. Effects of HLA-B27 on gut microbiota and dysbiosis in SpA are highly dependent on host genetic background and/or environment despite convergence of dysregulated immune pathways. These results indicate an ecological model of dysbiosis where the effects of multiple microbes contribute to the aberrant immune response, rather than a single or small number of microbes driving pathogenesis. This article is protected by copyright. All rights reserved.

All Authors:
Tejpal Gill,Mark Asquith,Stephen R Brooks,James T Rosenbaum,Robert A Colbert

First Authors:
Tejpal Gill

Correspondence:
Robert A Colbert

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