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IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease
DC Field | Value | Language |
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dc.contributor.author | Ju, Ji-Min | - |
dc.contributor.author | Nam, Giri | - |
dc.contributor.author | Lee, Young-Kwan | - |
dc.contributor.author | Jung, Minho | - |
dc.contributor.author | Chang, Hanna | - |
dc.contributor.author | Kim, Woojin | - |
dc.contributor.author | Shon, Woo Jeong | - |
dc.contributor.author | Lim, Ji Young | - |
dc.contributor.author | Kim, Joo Young | - |
dc.contributor.author | Chang, Jun | - |
dc.contributor.author | Min, Chang Ki | - |
dc.contributor.author | Lee, Dong-Sup | - |
dc.contributor.author | Choi, Kyungho | - |
dc.contributor.author | Shin, Dong-Mi | - |
dc.contributor.author | Choi, Eun Young | - |
dc.date.accessioned | 2023-04-18T06:22:40Z | - |
dc.date.available | 2023-04-18T06:22:40Z | - |
dc.date.created | 2021-05-21 | - |
dc.date.issued | 2021-03-09 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, Vol.118 No.10, p. e2011170118 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://hdl.handle.net/10371/190057 | - |
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 Ly6C(low)Ly6G(hi) 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. | - |
dc.language | 영어 | - |
dc.publisher | National Academy of Sciences | - |
dc.title | IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease | - |
dc.type | Article | - |
dc.identifier.doi | 10.1073/pnas.2011170118 | - |
dc.citation.journaltitle | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.identifier.wosid | 000627429100020 | - |
dc.identifier.scopusid | 2-s2.0-85102327493 | - |
dc.citation.number | 10 | - |
dc.citation.startpage | e2011170118 | - |
dc.citation.volume | 118 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Lee, Dong-Sup | - |
dc.contributor.affiliatedAuthor | Choi, Kyungho | - |
dc.contributor.affiliatedAuthor | Shin, Dong-Mi | - |
dc.contributor.affiliatedAuthor | Choi, Eun Young | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | REGULATORY T-CELLS | - |
dc.subject.keywordPlus | INDOLEAMINE 2,3-DIOXYGENASE | - |
dc.subject.keywordPlus | DENDRITIC CELLS | - |
dc.subject.keywordPlus | RESPONSES | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | CONVERSION | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | INDUCTION | - |
dc.subject.keywordPlus | TOLERANCE | - |
dc.subject.keywordAuthor | IDO | - |
dc.subject.keywordAuthor | Gr-1+CD11b+cell | - |
dc.subject.keywordAuthor | myeloid-derived suppressor cell | - |
dc.subject.keywordAuthor | ROS | - |
dc.subject.keywordAuthor | GVHD | - |
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