For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
2
views
16
references
 Top references
cited by
5
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      262
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Mechanism of indoleamine 2, 3‐dioxygenase inhibiting cardiac allograft rejection in mice

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Indoleamine 2, 3‐dioxygenase (IDO)‐mediated regulation of tryptophan metabolism plays an important role in immune tolerance in transplantation, but it has not been elucidated which mechanism specifically induces the occurrence of immune tolerance. Our study revealed that IDO exerts immunosuppressive effects through two pathways in mouse heart transplantation, ‘tryptophan depletion’ and ‘tryptophan metabolite accumulation’. The synergism between IDO +DC and TC (tryptophan catabolic products) has stronger inhibitory effects on T lymphocyte proliferation and mouse heart transplant rejection than the two intervention factors alone, and significantly prolong the survival time of donor‐derived transplanted skin. This work demonstrates that the combination of IDO +DC and TC can induce immune tolerance to a greater extent, and reduce the rejection of transplanted organs.

          Related collections

          Most cited references16

          • Record: found
          • Abstract: found
          • Article: not found

          Indoleamine 2,3 dioxygenase and metabolic control of immune responses.

          David Munn, Andrew L Mellor (2013)
          Sustained access to nutrients is a fundamental biological need, especially for proliferating cells, and controlling nutrient supply is an ancient strategy to regulate cellular responses to stimuli. By catabolizing the essential amino acid TRP, cells expressing the enzyme indoleamine 2,3 dioxygenase (IDO) can mediate potent local effects on innate and adaptive immune responses to inflammatory insults. Here, we discuss recent progress in elucidating how IDO activity promotes local metabolic changes that impact cellular and systemic responses to inflammatory and immunological signals. These recent developments identify potential new targets for therapy in a range of clinical settings, including cancer, chronic infections, autoimmune and allergic syndromes, and transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.
          Article 0 comments Cited 413 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer.

            George Prendergast, Courtney Smith, Sunil Thomas … (2014)
            Genetic and pharmacological studies of indoleamine 2,3-dioxygenase (IDO) have established this tryptophan catabolic enzyme as a central driver of malignant development and progression. IDO acts in tumor, stromal and immune cells to support pathogenic inflammatory processes that engender immune tolerance to tumor antigens. The multifaceted effects of IDO activation in cancer include the suppression of T and NK cells, the generation and activation of T regulatory cells and myeloid-derived suppressor cells, and the promotion of tumor angiogenesis. Mechanistic investigations have defined the aryl hydrocarbon receptor, the master metabolic regulator mTORC1 and the stress kinase Gcn2 as key effector signaling elements for IDO, which also exerts a non-catalytic role in TGF-β signaling. Small-molecule inhibitors of IDO exhibit anticancer activity and cooperate with immunotherapy, radiotherapy or chemotherapy to trigger rapid regression of aggressive tumors otherwise resistant to treatment. Notably, the dramatic antitumor activity of certain targeted therapeutics such as imatinib (Gleevec) in gastrointestinal stromal tumors has been traced in part to IDO downregulation. Further, antitumor responses to immune checkpoint inhibitors can be heightened safely by a clinical lead inhibitor of the IDO pathway that relieves IDO-mediated suppression of mTORC1 in T cells. In this personal perspective on IDO as a nodal mediator of pathogenic inflammation and immune escape in cancer, we provide a conceptual foundation for the clinical development of IDO inhibitors as a novel class of immunomodulators with broad application in the treatment of advanced human cancer.
            Article 0 comments Cited 203 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Indolamine 2,3-dioxygenase is expressed in the CNS and down-regulates autoimmune inflammation.

              Erik Kwidzinski, Jörg Bunse, Orhan Aktas … (2005)
              The tryptophan (trp)-catabolizing enzyme indolamine 2,3-dioxygenase (IDO) is induced by the T helper 1 (Th 1) cytokine IFN-gamma during infections in various tissues including the brain. Recent studies demonstrated an immune modulatory function of this enzyme, since IDO-mediated depletion of trp hinders T cell proliferation, while its inhibition by 1-methyl-tryptophan (1-Mt) induces breakdown of immune tolerance in the placenta, leading to rejection of allogeneic concepti. Here, we tested IDO expression and function during experimental autoimmune encephalomyelitis (EAE) actively induced in adult SJL mice by immunization with PLP139-151. IDO activity (determined by HPLC analysis of the kynurenine/tryptophan ratio) was increased in the spleen during the preclinical phase, and within the brain and spinal cord at the onset of symptoms. Immunocytochemistry revealed macrophages/activated microglia expressing IDO during EAE and in vitro experiments confirmed IDO induction in microglia upon IFN-gamma treatment with synergistic effects of TNF-alpha. Inhibition of IDO by systemic administration of 1-Mt at clinical onset significantly exacerbated disease scores. From these data, it is tempting to speculate that IFN-gamma from encephalitogenic Th 1 cells induces local IDO expression, thereby initiating a negative feedback loop which may underlie the self-limitation of autoimmune inflammation during EAE and multiple sclerosis.
              Article 0 comments Cited 75 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Tong Liu: liutonga@126.com
                Xiangchen Dai: mzzlee@163.com
                Journal
                Journal ID (nlm-ta): J Cell Mol Med
                Journal ID (iso-abbrev): J. Cell. Mol. Med
                Journal ID (doi): 10.1111/(ISSN)1582-4934
                Journal ID (publisher-id): JCMM
                Title: Journal of Cellular and Molecular Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 1582-1838
                ISSN (Electronic): 1582-4934
                Publication date (Electronic): 06 February 2020
                Publication date (Print): March 2020
                Volume: 24
                Issue: 6 ( doiID: 10.1111/jcmm.v24.6 )
                Pages: 3438-3448
                Affiliations
                [ 1 ] Department of General Surgery Tianjin General Surgery Institute Tianjin Medical University General Hospital Heping District China
                Author notes
                [*] [* ] Correspondence

                Xiangchen Dai, Tong Liu, Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China.

                Emails: mzzlee@ 123456163.com ; liutonga@ 123456126.com

                Author information
                https://orcid.org/0000-0001-5314-6618
                Article
                Publisher ID: JCMM15024
                DOI: 10.1111/jcmm.15024
                PMC ID: 7131949
                PubMed ID: 32027774
                SO-VID: 82694257-322f-4bec-be29-0781611b04f1
                Copyright © © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 10 July 2019
                Date revision received : 23 November 2019
                Date accepted : 21 December 2019
                Page count
                Figures: 6, Tables: 2, Pages: 11, Words: 6193
                Funding
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100011002;
                Award ID: 81070377
                Categories
                Subject: Original Article
                Subject: Original Articles
                Custom metadata
                source-schema-version-number 2.0
                cover-date March 2020
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.9 mode:remove_FC converted:05.04.2020

                ScienceOpen disciplines: Molecular medicine
                Keywords: allograft rejection,cardiac transplantation,immune tolerance,indoleamine 2,3‐dioxygenase
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: allograft rejection, cardiac transplantation, immune tolerance, indoleamine 2,3‐dioxygenase

                Comments

                Comment on this article

                scite_

                Similar content262

                See all similar

                Cited by5

                See all cited by

                Most referenced authors249

                See all reference authors