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World J Transplant. Jun 28, 2019; 9(2): 27-34
Published online Jun 28, 2019. doi: 10.5500/wjt.v9.i2.27
Immunometabolism: A target for the comprehension of immune response toward transplantation
Omar Domínguez-Amorocho, Tatiana Takiishi, Flavia Franco da Cunha, Niels Olsen Saraiva Camara
Omar Domínguez-Amorocho, Tatiana Takiishi, Flavia Franco da Cunha, Niels Olsen Saraiva Camara, Department of Immunology, Biomedical Sciences Institute, University of São Paulo, São Paulo 05508-900, Brazil
Author contributions: Domínguez-Amorocho O and Takiishi T contributed equally to this work, generated the figures and wrote the manuscript; da Cunha FF contributed to the writing of the manuscript; Camara NOS designed the aim of the editorial and wrote the manuscript.
Supported by FAPESP doctoral fellowship grants (Omar Dominguez-Amorocho and Flavia Cunha), No. 2017/05264-7; and PNPd postdoctoral fellowship grant (Tatiana Takiishi).
Conflict-of-interest statement: The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Niels Olsen Saraiva Câmara, MD, PhD, Research Scientist, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1730 Cid. Universitaria, Sao Paulo 05508-000, Brazil. niels@icb.usp.br
Telephone: +55-11-30917388
Received: September 12, 2018
Peer-review started: September 12, 2018
First decision: October 5, 2018
Revised: October 25, 2018
Accepted: January 28, 2019
Article in press: January 28, 2019
Published online: June 28, 2019
Abstract

Organ transplantation is a life-saving procedure, however predicting graft survival is still challenging. Understanding immune-cell pathobiology is critical to the development of effective therapies to prevent rejection. Over the recent years it has become progressively evident that the complex nature of immune cell behavioral dynamics is strongly dependent on cellular metabolism, which in turn, relies on competition for nutrients, oxygen and metabolites with other immune cells and microbiota. Furthermore, the influence of the inflammatory state can lead to substantial changes in conditions within the tissue micro-environment. Considering the context of immunity, alterations in metabolic pathways (glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, the fatty acid oxidation and synthesis, and the amino acid metabolic pathways) will influence the production of different sets of cytokines and affect transplantation outcome. It is now known that naïve, resting and effector cells acquire different metabolic profiles and studies have shown that specifically targeting some of these metabolic routes can prevent differentiation of effector T cells in favor of Tregs. Ultimately, to develop effective therapies that will prevent graft loss and understanding how cell metabolism impacts the fate and function of immune cells is now a critical point of discussion. The distinct metabolic features and requirements observed in effector and suppressive cell subsets offer promising opportunities for selective regulation of the immune responses in transplantation and will be discussed in this review.

Keywords: Transplantation, Metabolic processes, Immune tolerance, Metabolic activation, Inflammatory response

Core tip: In this review we summarize the most recent findings on metabolic pathways involved in the determination of immune cell fate and highlight the relevance of understanding how metabolic reprogramming is involved in the activation of dendritic cells and T cells, as well as development of strategies that target metabolic reprogramming to counteract effector cell activation in order to prevent graft failure.