Gerald Brandacher1, Raimund Margreiter, Dietmar Fuchs. 1. Department of General and Transplant Surgery, D. Swarovski Research Laboratory, Innsbruck Medical University, Austria. gerald.brandacher@uki.at
Abstract
PURPOSE OF REVIEW: The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is activated by interferon-gamma and via tryptophan depletion and the production of proapoptotic downstream metabolites IDO suppresses adaptive T-cell-mediated immunity in inflammation, host immune defence and maternal tolerance. In addition, IDO-mediated tryptophan catabolism occurring in dendritic cells is an emerging potent mechanism of peripheral tolerance. RECENT FINDINGS: Recent data dissecting the molecular T-cell regulatory mechanisms and immunomodulatory features of IDO have given rise to the development of new concepts for translating such naturally occurring tolerance mechanisms of IDO into the service of permanent graft acceptance, thereby eventually facilitating the ultimate goal in transplantation of donor antigen-specific unresponsiveness. SUMMARY: This review focuses on the nature and mechanisms of IDO-mediated immune regulation in alloimmunity and transplantation and outlines its clinical relevance and therapeutic implications.
PURPOSE OF REVIEW: The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is activated by interferon-gamma and via tryptophan depletion and the production of proapoptotic downstream metabolites IDO suppresses adaptive T-cell-mediated immunity in inflammation, host immune defence and maternal tolerance. In addition, IDO-mediated tryptophan catabolism occurring in dendritic cells is an emerging potent mechanism of peripheral tolerance. RECENT FINDINGS: Recent data dissecting the molecular T-cell regulatory mechanisms and immunomodulatory features of IDO have given rise to the development of new concepts for translating such naturally occurring tolerance mechanisms of IDO into the service of permanent graft acceptance, thereby eventually facilitating the ultimate goal in transplantation of donor antigen-specific unresponsiveness. SUMMARY: This review focuses on the nature and mechanisms of IDO-mediated immune regulation in alloimmunity and transplantation and outlines its clinical relevance and therapeutic implications.
Authors: Vikas R Dharnidharka; Sushil Gupta; Eihab Al Khasawneh; Allah Haafiz; Jonathan J Shuster; Douglas W Theriaque; Amir H Shahlaee; Timothy J Garrett Journal: Pediatr Transplant Date: 2011-02-24
Authors: Eihab Al Khasawneh; Sushil Gupta; Sanjeev Y Tuli; Amir H Shahlaee; Timothy J Garrett; Kenneth B Schechtman; Vikas R Dharnidharka Journal: Pediatr Transplant Date: 2014-02-01
Authors: Vikas R Dharnidharka; Eihab Al Khasawneh; Sushil Gupta; Jonathan J Shuster; Douglas W Theriaque; Amir H Shahlaee; Timothy J Garrett Journal: Transplantation Date: 2013-09 Impact factor: 4.939
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