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      The modulation of enzyme indoleamine 2,3-dioxygenase from dendritic cells for the treatment of type 1 diabetes mellitus

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          Abstract

          Diabetes mellitus type 1 (DM1) is an autoimmune disease in which β-cells of the pancreas islet are destroyed by T lymphocytes. Specific T cells are activated by antigen-presenting cells, mainly dendritic cells (DCs). It is already known that the regulation of tryptophan pathway in DC can be a mechanism of immunomodulation. The enzyme indoleamine 2,3-dioxygenase (IDO) is present in many cells, including DC, and participates in the metabolism of the amino acid tryptophan. Recent studies suggest the involvement of IDO in the modulation of immune response, which became more evident after the in vitro demonstration of IDO production by DC and of the ability of these cells to inhibit lymphocyte function through the control of tryptophan metabolism. Current studies on immunotherapies describe the use of DC and IDO to control the progression of the immune response that triggers DM1. The initial results obtained are promising and indicate the possibility of developing therapies for the treatment or prevention of the DM1. Clinical trials using these cells in DM1 patients represent an interesting alternative treatment. However, clinical trials are still in the initial phase and a robust group of assays is necessary.

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          Taking dendritic cells into medicine.

          Dendritic cells (DCs) orchestrate a repertoire of immune responses that bring about resistance to infection and silencing or tolerance to self. In the settings of infection and cancer, microbes and tumours can exploit DCs to evade immunity, but DCs also can generate resistance, a capacity that is readily enhanced with DC-targeted vaccines. During allergy, autoimmunity and transplant rejection, DCs instigate unwanted responses that cause disease, but, again, DCs can be harnessed to silence these conditions with novel therapies. Here we present some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy.
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            IDO expression by dendritic cells: tolerance and tryptophan catabolism.

            Indoleamine 2,3-dioxygenase (IDO) is an enzyme that degrades the essential amino acid tryptophan. The concept that cells expressing IDO can suppress T-cell responses and promote tolerance is a relatively new paradigm in immunology. Considerable evidence now supports this hypothesis, including studies of mammalian pregnancy, tumour resistance, chronic infections and autoimmune diseases. In this review, we summarize key recent developments and propose a unifying model for the role of IDO in tolerance induction.
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              Indoleamine 2,3 dioxygenase and metabolic control of immune responses.

              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.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                24 July 2017
                : 11
                : 2171-2178
                Affiliations
                [1 ]Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Cidade Universitária Zeferino Vaz, Campinas, SP, Brazil
                [2 ]Department of Biomedical Science, Faculty of Americana, Americana, SP, Brazil
                [3 ]Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil
                [4 ]Department of Biochemistry and Microbiology, Institute of Biosciences, Universidade Estadual Paulista, UNESP, Rio Claro, SP, Brazil
                Author notes
                Correspondence: Patrícia Ucelli Simioni, Department of Biochemistry and Microbiology, Institute of Biological Sciences, São Paulo State University, UNESP/Rio Claro, Av. 24-A, 1515 Bela Vista, zipcode 13506-900, Rio Claro, SP, Brazil, Tel +55 199 9699 1899, Email psimioni@ 123456gmail.com
                Article
                dddt-11-2171
                10.2147/DDDT.S135367
                5533566
                99ec2585-b6db-4631-b094-a7d5fe7532b6
                © 2017 Abram et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Categories
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                Pharmacology & Pharmaceutical medicine
                autoimmunity,immunoregulation,diabetes mellitus type 1,clinical trials,dendritic cells,indoleamine,tryptophan,tolerance

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