气候变化领域集成服务门户(CCPortal): IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease

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DOI	10.1073/pnas.2011170118
	IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease
	Ju J.-M.; Nam G.; Lee Y.-K.; Jung M.; Chang H.; Kim W.; Shon W.J.; Lim J.Y.; Kim J.Y.; Chang J.; Min C.K.; Lee D.-S.; Choi K.; Shin D.-M.; Choi E.Y.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) also has an immunological function to suppress T cell activation in inflammatory circumstances, including graft-versus-host disease (GVHD), a fatal complication after allogeneic bone marrow transplantation (allo-BMT). Although the mononuclear cell expression of IDO1 has been associated with improved outcomes in GVHD, the underlying mechanisms remain unclear. Herein, we used IDO-deficient (Ido1-/-) BMT to understand why myeloid IDO limits the severity of GVHD. Hosts with Ido1-/- BM exhibited increased lethality, with enhanced proinflammatory and reduced regulatory T cell responses compared with wild type (WT) allo-BMT controls. Despite the comparable expression of the myeloid-derived suppressor cell (MDSC) mediators, arginase-1, inducible nitric oxide synthase, and interleukin 10, Ido1-/- Gr-1+CD11b+ cells from allo-BMT or in vitro BM culture showed compromised immune-suppressive functions and were skewed toward the Ly6ClowLy6Ghi subset, compared with the WT counterparts. Importantly, Ido1-/-Gr-1+CD11b+ cells exhibited elevated levels of reactive oxygen species (ROS) and neutrophil numbers. These characteristics were rescued by human IDO1 with intact heme-binding and catalytic activities and were recapitulated by the treatment of WT cells with the IDO1 inhibitor L1-methyl tryptophan. ROS scavenging by N-acetylcysteine reverted the Ido1-/-Gr-1+CD11b+ composition and function to an MDSC state, as well as improved the survival of GVHD hosts with Ido1-/- BM. In summary, myeloid-derived IDO1 enhances GVHD survival by regulating ROS levels and limiting the ability of Gr-1+CD11b+ MDSCs to differentiate into proinflammatory neutrophils. Our findings provide a mechanistic insight into the immune-regulatory roles of the metabolic enzyme IDO1. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Gr-1+CD11b+ cell; GVHD; IDO; Myeloid-derived suppressor cell; ROS
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180370
作者单位	Department of Biomedical Sciences, Seoul National University College of Medicine, Chongno-gu, Seoul, 03080, South Korea; Institute of Human Environment Interface Biology, Seoul National University College of Medicine, Chongno-gu, Seoul, 03080, South Korea; Department of Food and Nutrition, Seoul National University College of Human Ecology, Gwanak-gu, Seoul, 08826, South Korea; Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seocho-gu, Seoul, 06591, South Korea; Department of Pharmacy, Ewha University, Seodaemun-gu, Seoul, 03760, South Korea
推荐引用方式 GB/T 7714	Ju J.-M.,Nam G.,Lee Y.-K.,et al. IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease[J],2021,118(10).
APA	Ju J.-M..,Nam G..,Lee Y.-K..,Jung M..,Chang H..,...&Choi E.Y..(2021).IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Ju J.-M.,et al."IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).