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

Authors Abram DM, Fernandes LGR, Ramos Filho ACS, Simioni PU

Received 22 February 2017

Accepted for publication 7 May 2017

Published 24 July 2017 Volume 2017:11 Pages 2171—2178

DOI https://doi.org/10.2147/DDDT.S135367

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Professor Manfred Ogris

Débora Moitinho Abram,1 Luis Gustavo Romani Fernandes,1,2 Antônio Celso Saragossa Ramos Filho,2 Patrícia Ucelli Simioni2–4

1Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Cidade Universitária Zeferino Vaz, Campinas, SP, Brazil; 2Department of Biomedical Science, Faculty of Americana, Americana, SP, Brazil; 3Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil; 4Department of Biochemistry and Microbiology, Institute of Biosciences, Universidade Estadual Paulista, UNESP, Rio Claro, SP, Brazil

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.

Keywords: autoimmunity, immunoregulation, diabetes mellitus type 1, clinical trials, dendritic cells, indoleamine, tryptophan, tolerance

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