Perturbed Mucosal Immunity and Dysbiosis Accompany Clinical Disease in a Rat Model of Spondyloarthritis.
Perturbed Mucosal Immunity and Dysbiosis Accompany Clinical Disease in a Rat Model of Spondyloarthritis.
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DOI：
10.1002/art.39681
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Rosenbaum JT
中科院分区：
文献类型：
--
作者：
Asquith MJ;Stauffer P;Davin S;Mitchell C;Lin P;Rosenbaum JT
HLA-B27/β2微球蛋白（β 2 m）转基因大鼠是B27相关脊柱关节病的主要模型，疾病依赖于肠道细菌的存在。我们之前已经证明，成年HLA-B27/β 2 m大鼠的肠道微生物群发生了改变。在这项研究中，我们试图更好地定义年龄依赖性的变化，粘膜免疫功能和生态失调在这个模型。在断奶后（3周和6周）、疾病发作时（10周）和疾病建立后（16周），从野生型和HLA-B27/β 2 m+大鼠收集肠内容物。通过16 s测序和qRT-PCR确定微生物群落结构。通过流式细胞术分析粘液和全身性Th 1、Th 17和Treg应答，以及IgA包被的肠道细菌的频率。通过qRT-PCR测定炎性细胞因子和抗菌肽（AMP）的肠表达。在HLA-B27/β 2 m+大鼠中，在断奶后期间炎性细胞因子特征和AMP表达升高先于临床肠道炎症和生态失调的发展。在HLA-B27/β 2 m大鼠盲肠和结肠粘膜中特异性地观察到Th 17池的早期和持续扩增。强烈升高的嗜粘蛋白阿克曼氏菌定植和肠道细菌的伊加包被与HLA-B27表达和关节炎发展显著相关。该大鼠模型中的HLA-B27/β 2 m表达使宿主从婴儿期起对微生物抗原高度应答。HLA-B27/β 2 m +ve动物中先天免疫的早期激活和粘膜Th 17特征的扩增很快就会导致生态失调。在患病前和患病的SpA患者人群中，受干扰的粘膜免疫和微生态失调非常值得进一步研究。
The HLA-B27/β2 microglobulin (β2m) transgenic rat is a leading model of B27-associated spondyloarthopathy and disease is dependent on the presence of intestinal bacteria. We have shown previously that adult HLA-B27/β2m rats have an altered intestinal microbiota. In this study we sought to better define age-dependent changes to both mucosal immune function and dysbiosis in this model. Intestinal contents were collected from wild type and HLA-B27/β2m+ rats post-weaning (3 and 6 weeks), at disease onset (10 wks) and after the establishment of disease (16 wks). Microbial community structure was determined by 16s sequencing and qRT-PCR. Mucosal and systemic Th1, Th17 and Treg responses were analyzed by flow cytometry, as was the frequency of IgA-coated intestinal bacteria. Intestinal expression of inflammatory cytokines and antimicrobial peptides (AMPs) was determined by qRT-PCR. An inflammatory cytokine signature and elevated AMP expression during the post-weaning period preceded the development of clinical bowel inflammation and dysbiosis in HLA-B27/β2m+ rats. An early and sustained expansion of the Th17 pool was specifically observed in cecal and colonic mucosa of HLA-B27/β2m rats. Strongly elevated Akkermansia mucinphilia colonization and IgA coating of intestinal bacteria was significantly associated with HLA-B27 expression and arthritis development. HLA-B27/β2m expression in this rat model renders the host hyper-responsive to microbial antigens from infancy. Early activation of innate immunity and expansion of a mucosal Th17 signature are soon followed by dysbiosis in HLA-B27/β2m+ve animals. Perturbed mucosal immunity and dysbiosis strongly merit further study in both pre-diseased and diseased SpA patient populations.
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DOI：
10.1016/j.berh.2014.10.018
发表时间：
2014-10
期刊：
Best practice & research. Clinical rheumatology
影响因子：
--
作者：
Asquith M;Elewaut D;Lin P;Rosenbaum JT
通讯作者：
Rosenbaum JT
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
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Honda K
DOI：
10.1073/pnas.1219451110
发表时间：
2013-05-28
影响因子：
11.1
作者：
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通讯作者：
Cani, Patrice D.
影响因子：
5.2
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30.3
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Xavier RJ