Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 장준 | * |
dc.date.accessioned | 2021-05-28T16:30:37Z | - |
dc.date.available | 2021-05-28T16:30:37Z | - |
dc.date.issued | 2021 | * |
dc.identifier.issn | 0027-8424 | * |
dc.identifier.other | OAK-29157 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/257403 | - |
dc.description.abstract | 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. | * |
dc.language | English | * |
dc.publisher | National Academy of Sciences | * |
dc.subject | Gr-1+CD11b+ cell | * |
dc.subject | GVHD | * |
dc.subject | IDO | * |
dc.subject | Myeloid-derived suppressor cell | * |
dc.subject | ROS | * |
dc.title | IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease | * |
dc.type | Article | * |
dc.relation.issue | 10 | * |
dc.relation.volume | 118 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.journaltitle | Proceedings of the National Academy of Sciences of the United States of America | * |
dc.identifier.doi | 10.1073/pnas.2011170118 | * |
dc.identifier.wosid | WOS:000627429100020 | * |
dc.identifier.scopusid | 2-s2.0-85102327493 | * |
dc.author.google | Ju J.-M. | * |
dc.author.google | Nam G. | * |
dc.author.google | Lee Y.-K. | * |
dc.author.google | Jung M. | * |
dc.author.google | Chang H. | * |
dc.author.google | Kim W. | * |
dc.author.google | Shon W.J. | * |
dc.author.google | Lim J.Y. | * |
dc.author.google | Kim J.Y. | * |
dc.author.google | Chang J. | * |
dc.author.google | Min C.K. | * |
dc.author.google | Lee D.-S. | * |
dc.author.google | Choi K. | * |
dc.author.google | Shin D.-M. | * |
dc.author.google | Choi E.Y. | * |
dc.contributor.scopusid | 장준(8735999100) | * |
dc.date.modifydate | 20231120165756 | * |