The Gut Bacteria Dysbiosis Contributes to Chronic Graft-Versus-Host Disease Associated With a Treg/Th1 Ratio Imbalance.
The Gut Bacteria Dysbiosis Contributes to Chronic Graft-Versus-Host Disease Associated With a Treg/Th1 Ratio Imbalance.
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肠道细菌失调导致与 Treg/Th1 比例失衡相关的慢性移植物抗宿主病
DOI：
10.3389/fmicb.2022.813576
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发表时间：
2022
影响因子：
5.2
通讯作者：
Weng, Jianyu
中科院分区：
文献类型：
--
作者：
Wang, Yulian;Huang, Lisi;Huang, Tian;Geng, Suxia;Chen, Xiaomei;Huang, Xin;Lai, Peilong;Du, Xin;Weng, Jianyu
肠道菌群失调已在大量自身免疫性疾病中发现。然而，肠道细菌在慢性硬皮病移植物抗宿主病（Scl-GVHD）小鼠模型中的影响仍然难以捉摸，Scl-GVHD是一种类似于以多个器官（如皮肤）的慢性炎症为特征的自身免疫性疾病的疾病。在这里，我们探讨了肠道细菌在Scl-cGVHD小鼠模型中的作用。建立Scl-cGVHD小鼠模型，采集粪便植物群，采用16 SrDNA扩增子测序法分析肠道植物群的组成和多样性，并检测Scl-cGVHD小鼠脾细胞中Treg和Th 1细胞的比例。为验证Scl-cGVHD肠道植物群的免疫调节作用，我们制备了Scl-cGVHD肠道菌群提取物，与脾细胞体外共培养，采用流式细胞仪检测T细胞分化和细胞因子分泌。通过检查cGVHD小鼠脾细胞中的T细胞分化，我们发现在cGVHD小鼠中Treg细胞显著减少（15.27 ± 0.23对12.23 ± 0.47，p = 0.0045），而Th 1细胞增加（1.54 ± 0.18对6.68 ± 0.80，p = 0.0034）。Scl-cGVHD小鼠肠道细菌的组成和多样性与无GVHD小鼠相比存在显著差异。小鼠粪便细菌样品的分析（n = 10，5个Scl-cGVHD和5个非GVHD）显示Scl-cGVHD和非GVHD小鼠中的显著分离[R = 0.732，p = 0.015，非参数分析（ANOSIM）]。在Scl-cGVHD小鼠中，瘤胃球菌科和属细菌的丰度减少，毛螺菌科和限于物种毛螺菌科_细菌_DW 17的丰度增加。细胞水平研究的体外结果表明，Scl-cGVHD小鼠肠道菌群的细菌提取物调节脾T细胞向CD 4 +IFN-γ+ Th 1细胞分化（14.37 ± 0.32对比10.40 ± 2.19，p = 0.036），并且与非GVHD小鼠相比，CD 4 + CD 25 + Foxp 3 + T细胞百分比降低（6.36 ± 0.39对比8.66 ± 0.07，p = 0.001）。此外，补充细胞培养物中促炎性干扰素- γ（IFN-γ）细胞因子的分泌增加（4，898.58 ± 235.82 vs.4，347.87 ± 220.02 pg/ml，p = 0.042），但抗炎性白细胞介素（IL）-10降低（7，636.57 ± 608.05 vs 9，563.56 ± 603.34 pg/ml，p = 0.018）。我们的数据显示了Scl-cGVHD小鼠肠道细菌的不同组成和多样性。肠道菌群失调可能调节Treg和Th 1细胞的分化比例，与Scl-cGVHD的发生有关。
Dysbiosis of gut bacteria has been discovered in a large number of autoimmune diseases. However, the influence of the gut bacteria in the mice model of chronic sclerodermatous graft-versus-host disease (Scl-GVHD), a disease that resembles an autoimmune disease characterized by chronic inflammation of multiple organs, such as skin, remains elusive. Here, we explore the role of gut bacteria in an Scl-cGVHD mice model. We established a mouse model of Scl-cGVHD, collected fecal flora, analyzed the composition, and diversity of intestinal flora using 16S rDNA amplicon sequencing, and detected the proportion of Treg and Th1 cells in splenocytes of Scl-cGVHD mice. To verify the immunoregulatory effect of Scl-cGVHD intestinal flora, we prepared bacterial extracts, co-cultured with splenocytes in vitro, and used flow cytometry to detect T cell differentiation and cytokine secretion. By examining T-cell differentiation in splenocytes of cGVHD mice, we found that Treg cells were significantly reduced (15.27 ± 0.23 vs. 12.23 ± 0.47, p = 0.0045) and Th1 cells were increased (1.54 ± 0.18 vs. 6.68 ± 0.80, p = 0.0034) in cGVHD mice. Significant differences were observed in the composition and diversity of the gut bacteria in mice with Scl-cGVHD versus without GVHD. Analysis of mice fecal bacteria samples (n = 10, 5 Scl-cGVHD and 5 Non-GVHD) showed significant separation [R = 0.732, p = 0.015, non-parametric analysis (ANOSIM)] in Scl-cGVHD and non-GVHD mice. The abundance of the family and genus Ruminococcaceae bacteria decreased and the family Lachnospiraceae and limited to the species Lachnospiraceae_bacterium_DW17 increased in Scl-cGVHD mice. In vitro results of the cellular level study suggest that the bacteria extracts of gut microbiota from Scl-cGVHD mice modulated the splenic T cells toward differentiation into CD4+IFN-γ+ Th1 cells (14.37 ± 0.32 vs. 10.40 ± 2.19, p = 0.036), and the percentage of CD4+CD25+Foxp3+ Tregs decreased (6.36 ± 0.39 vs. 8.66 ± 0.07, p = 0.001) compared with the non-GVHD mice. In addition, the secretion of proinflammatory interferon- γ (IFN-γ) cytokine in the supplement of cellular culture was increased (4,898.58 ± 235.82 vs. 4,347.87 ± 220.02 pg/ml, p = 0.042) in the mice model of the Scl-cGVHD group, but anti-inflammatory interleukin (IL)-10 decreased (7,636.57 ± 608.05 vs. 9,563.56 ± 603.34 pg/ml, p = 0.018). Our data showed the different composition and diversity of gut bacteria in the Scl-cGVHD mice. The dysbiosis of gut bacteria may regulate the differentiation ratio of Treg and Th1 cells, which was associated with Scl-cGVHD.
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DOI：
10.1016/j.bbmt.2014.10.029
发表时间：
2015-01
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Sarantopoulos S;Blazar BR;Cutler C;Ritz J
通讯作者：
Ritz J
影响因子：
30.5
作者：
Mathewson ND;Jenq R;Mathew AV;Koenigsknecht M;Hanash A;Toubai T;Oravecz-Wilson K;Wu SR;Sun Y;Rossi C;Fujiwara H;Byun J;Shono Y;Lindemans C;Calafiore M;Schmidt TM;Honda K;Young VB;Pennathur S;van den Brink M;Reddy P
通讯作者：
Reddy P
影响因子：
28.5
作者：
Ruggeri A;Labopin M;Bacigalupo A;Afanasyev B;Cornelissen JJ;Elmaagacli A;Itälä-Remes M;Blaise D;Meijer E;Koc Y;Milpied N;Schouten HC;Kroeger N;Mohty M;Nagler A
通讯作者：
Nagler A
DOI：
10.1084/jem.20112408
发表时间：
2012-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jenq RR;Ubeda C;Taur Y;Menezes CC;Khanin R;Dudakov JA;Liu C;West ML;Singer NV;Equinda MJ;Gobourne A;Lipuma L;Young LF;Smith OM;Ghosh A;Hanash AM;Goldberg JD;Aoyama K;Blazar BR;Pamer EG;van den Brink MR
通讯作者：
van den Brink MR
影响因子：
16.6
作者：
Jangi S;Gandhi R;Cox LM;Li N;von Glehn F;Yan R;Patel B;Mazzola MA;Liu S;Glanz BL;Cook S;Tankou S;Stuart F;Melo K;Nejad P;Smith K;Topçuolu BD;Holden J;Kivisäkk P;Chitnis T;De Jager PL;Quintana FJ;Gerber GK;Bry L;Weiner HL
通讯作者：
Weiner HL