小柯机器人

美国华盛顿大学Geoffrey R. Hill研究组发现，肠道微生物群控制移植物抗宿主病(GVHD)独立于供宿主遗传差异。2023年7月21日，国际知名学术期刊《免疫》发表了这一成果。

他们证明了不同供应商来源的基因相同的小鼠具有明显不同的肠道微生物群和回肠MHC II类(MHC-II)表达，导致GVHD严重程度不一致。他们利用同笼饲养和抗生素治疗来表征与MHC-II表达呈正相关和负相关的细菌分类群。大部分细菌MHC-II诱导剂对万古霉素敏感，移植前后口服万古霉素可减弱CD4+ T细胞介导的GVHD。

在一个大型临床干细胞移植(SCT)队列中，他们发现移植前微生物、HLA II类表达、GVHD和死亡率之间存在类似的关系。这些数据强调了移植前微生物类群独立于遗传差异导致GVHD的治疗机制。

研究人员表示，急性移植物抗宿主病(aGVHD)仍然是同种异体SCT的主要限制，严重的肠道表现是早期死亡的主要原因。肠道微生物群通过回肠上皮细胞(IECs)控制MHC-II的表达，从而促进GVHD。

附：英文原文

Title: Intestinal microbiota controls graft-versus-host disease independent of donor-host genetic disparity

Author: Motoko Koyama, Daniel S. Hippe, Sujatha Srinivasan, Sean C. Proll, Oriana Miltiadous, Naisi Li, Ping Zhang, Kathleen S. Ensbey, Noah G. Hoffman, Christine R. Schmidt, Albert C. Yeh, Simone A. Minnie, Susan M. Strenk, Tina L. Fiedler, Namita Hattangady, Jacob Kowalsky, Willian M. Grady, Mariapia A. Degli-Esposti, Antiopi Varelias, Andrew D. Clouston, Marcel R.M. van den Brink, Neelendu Dey, Timothy W. Randolph, Kate A. Markey, David N. Fredricks, Geoffrey R. Hill

Issue&Volume: 2023-07-21

Abstract: Acute graft-versus-host disease (aGVHD) remains a major limitation of allogeneic stem cell transplantation (SCT), and severe intestinal manifestation is the major cause of early mortality. Intestinal microbiota control MHC class II (MHC-II) expression by ileal intestinal epithelial cells (IECs) that promote GVHD. Here, we demonstrated that genetically identical mice of differing vendor origins had markedly different intestinal microbiota and ileal MHC-II expression, resulting in discordant GVHD severity. We utilized cohousing and antibiotic treatment to characterize the bacterial taxa positively and negatively associated with MHC-II expression. A large proportion of bacterial MHC-II inducers were vancomycin sensitive, and peri-transplant oral vancomycin administration attenuated CD4+ T cell-mediated GVHD. We identified a similar relationship between pre-transplant microbes, HLA class II expression, and both GVHD and mortality in a large clinical SCT cohort. These data highlight therapeutically tractable mechanisms by which pre-transplant microbial taxa contribute to GVHD independently of genetic disparity.

DOI: 10.1016/j.immuni.2023.06.024

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00281-9

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