美国密歇根大学Pavan Reddy团队发现，异基因干细胞移植后环境氧水平调节肠道稳态失调和移植物抗宿主病（GVHD）严重程度。相关论文于2023年2月2日发表在《免疫》杂志上。

他们在胃肠道（GI）GVHD的多种特异性无病原体（SPF），少量微生物和无菌小鼠模型中表明，致病性T细胞启动肠道损伤改变了GI中的环境氧水平并导致生理失调。氧水平的变化有助于宿主肠道HIF-1α-和微生物组依赖性方式的肠道病理严重程度。口服铁螯合剂调节肠道环境氧水平可缓解生理失调并降低GI GVHD 的严重程度。因此，靶向环境肠道氧气水平可能成为一种新的非免疫抑制策略，以减轻T细胞驱动的肠道疾病。

据悉，T 细胞介导的GI疾病（例如GVHD和炎症性肠病）的严重程度与宿主肠道微生物组组成多样性的减少相关，其特征是专性厌氧共生体的丧失。支持微生物结构这些变化的机制仍然未知。

附：英文原文

Title: Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation

Author: Keisuke Seike, Anders Kiledal, Hideaki Fujiwara, Israel Henig, Marina Burgos da Silva, Marcel R.M. van den Brink, Robert Hein, Matthew Hoostal, Chen Liu, Katherine Oravecz-Wilson, Emma Lauder, Lu Li, Yaping Sun, Thomas M. Schmidt, Yatrik M. Shah, Robert R. Jenq, Gregory Dick, Pavan Reddy

Issue&Volume: 2023-02-02

Abstract: The severity of T cell-mediated gastrointestinal (GI) diseases such as graft-versus-hostdisease (GVHD) and inflammatory bowel diseases correlates with a decrease in the diversityof the host gut microbiome composition characterized by loss of obligate anaerobiccommensals. The mechanisms underpinning these changes in the microbial structure remainunknown. Here, we show in multiple specific pathogen-free (SPF), gnotobiotic, andgerm-free murine models of GI GVHD that the initiation of the intestinal damage bythe pathogenic T cells altered ambient oxygen levels in the GI tract and caused dysbiosis.The change in oxygen levels contributed to the severity of intestinal pathology ina host intestinal HIF-1α- and a microbiome-dependent manner. Regulation of intestinalambient oxygen levels with oral iron chelation mitigated dysbiosis and reduced theseverity of the GI GVHD. Thus, targeting ambient intestinal oxygen levels may representa novel, non-immunosuppressive strategy to mitigate T cell-driven intestinal diseases.

DOI: 10.1016/j.immuni.2023.01.007

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00017-1