失调
生物
免疫学
微生物群
移植
肠粘膜
移植物抗宿主病
干细胞
专性厌氧菌
胃肠道
肠道菌群
内科学
无氧运动
医学
生理学
生物信息学
生物化学
遗传学
作者
Keisuke Seike,E. Anders Kiledal,Hideaki Fujiwara,Israel Henig,Marina Burgos da Silva,Marcel R.M. van den Brink,Robert Hein,Matthew J. Hoostal,Chen Liu,Katherine Oravecz-Wilson,Emma Lauder,Li Lü,Yaping Sun,Thomas M. Schmidt,Yatrik M. Shah,Robert R. Jenq,Gregory J. Dick,Pavan Reddy
出处
期刊:Immunity
[Elsevier]
日期:2023-02-01
卷期号:56 (2): 353-368.e6
被引量:8
标识
DOI:10.1016/j.immuni.2023.01.007
摘要
The severity of T cell-mediated gastrointestinal (GI) diseases such as graft-versus-host disease (GVHD) and inflammatory bowel diseases correlates with a decrease in the diversity of the host gut microbiome composition characterized by loss of obligate anaerobic commensals. The mechanisms underpinning these changes in the microbial structure remain unknown. Here, we show in multiple specific pathogen-free (SPF), gnotobiotic, and germ-free murine models of GI GVHD that the initiation of the intestinal damage by the 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 in a host intestinal HIF-1α- and a microbiome-dependent manner. Regulation of intestinal ambient oxygen levels with oral iron chelation mitigated dysbiosis and reduced the severity of the GI GVHD. Thus, targeting ambient intestinal oxygen levels may represent a novel, non-immunosuppressive strategy to mitigate T cell-driven intestinal diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI