Immunometabolic Therapeutic Targets of Graft-versus-Host Disease (GvHD)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option in the treatment of aggressive malignant and non-malignant blood disorders. However, the benefits of allo-HSCT can be compromised by graft-versus-host disease (GvHD), a prevalent and morbid complication of allo-HSCT....

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Autores principales:	Kudakwashe Mhandire, Komalpreet Saggu, Nataliya Prokopenko Buxbaum
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	GvHD T cells metabolism therapeutic targets glycolysis fatty acid oxidation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/29acf0cc43d042a39fc74b9001240bf1
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spelling	oai:doaj.org-article:29acf0cc43d042a39fc74b9001240bf12021-11-25T18:20:33ZImmunometabolic Therapeutic Targets of Graft-versus-Host Disease (GvHD)10.3390/metabo111107362218-1989https://doaj.org/article/29acf0cc43d042a39fc74b9001240bf12021-10-01T00:00:00Zhttps://www.mdpi.com/2218-1989/11/11/736https://doaj.org/toc/2218-1989Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option in the treatment of aggressive malignant and non-malignant blood disorders. However, the benefits of allo-HSCT can be compromised by graft-versus-host disease (GvHD), a prevalent and morbid complication of allo-HSCT. GvHD occurs when donor immune cells mount an alloreactive response against host antigens due to histocompatibility differences between the donor and host, which may result in extensive tissue injury. The reprogramming of cellular metabolism is a feature of GvHD that is associated with the differentiation of donor CD4+ cells into the pathogenic Th1 and Th17 subsets along with the dysfunction of the immune-suppressive protective T regulatory cells (Tregs). The activation of glycolysis and glutaminolysis with concomitant changes in fatty acid oxidation metabolism fuel the anabolic activities of the proliferative alloreactive microenvironment characteristic of GvHD. Thus, metabolic therapies such as glycolytic enzyme inhibitors and fatty acid metabolism modulators are a promising therapeutic strategy for GvHD. We comprehensively review the role of cellular metabolism in GvHD pathogenesis, identify candidate therapeutic targets, and describe potential strategies for augmenting immunometabolism to ameliorate GvHD.Kudakwashe MhandireKomalpreet SagguNataliya Prokopenko BuxbaumMDPI AGarticleGvHDT cellsmetabolismtherapeutic targetsglycolysisfatty acid oxidationMicrobiologyQR1-502ENMetabolites, Vol 11, Iss 736, p 736 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	GvHD T cells metabolism therapeutic targets glycolysis fatty acid oxidation Microbiology QR1-502
spellingShingle	GvHD T cells metabolism therapeutic targets glycolysis fatty acid oxidation Microbiology QR1-502 Kudakwashe Mhandire Komalpreet Saggu Nataliya Prokopenko Buxbaum Immunometabolic Therapeutic Targets of Graft-versus-Host Disease (GvHD)
description	Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option in the treatment of aggressive malignant and non-malignant blood disorders. However, the benefits of allo-HSCT can be compromised by graft-versus-host disease (GvHD), a prevalent and morbid complication of allo-HSCT. GvHD occurs when donor immune cells mount an alloreactive response against host antigens due to histocompatibility differences between the donor and host, which may result in extensive tissue injury. The reprogramming of cellular metabolism is a feature of GvHD that is associated with the differentiation of donor CD4+ cells into the pathogenic Th1 and Th17 subsets along with the dysfunction of the immune-suppressive protective T regulatory cells (Tregs). The activation of glycolysis and glutaminolysis with concomitant changes in fatty acid oxidation metabolism fuel the anabolic activities of the proliferative alloreactive microenvironment characteristic of GvHD. Thus, metabolic therapies such as glycolytic enzyme inhibitors and fatty acid metabolism modulators are a promising therapeutic strategy for GvHD. We comprehensively review the role of cellular metabolism in GvHD pathogenesis, identify candidate therapeutic targets, and describe potential strategies for augmenting immunometabolism to ameliorate GvHD.
format	article
author	Kudakwashe Mhandire Komalpreet Saggu Nataliya Prokopenko Buxbaum
author_facet	Kudakwashe Mhandire Komalpreet Saggu Nataliya Prokopenko Buxbaum
author_sort	Kudakwashe Mhandire
title	Immunometabolic Therapeutic Targets of Graft-versus-Host Disease (GvHD)
title_short	Immunometabolic Therapeutic Targets of Graft-versus-Host Disease (GvHD)
title_full	Immunometabolic Therapeutic Targets of Graft-versus-Host Disease (GvHD)
title_fullStr	Immunometabolic Therapeutic Targets of Graft-versus-Host Disease (GvHD)
title_full_unstemmed	Immunometabolic Therapeutic Targets of Graft-versus-Host Disease (GvHD)
title_sort	immunometabolic therapeutic targets of graft-versus-host disease (gvhd)
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/29acf0cc43d042a39fc74b9001240bf1
work_keys_str_mv	AT kudakwashemhandire immunometabolictherapeutictargetsofgraftversushostdiseasegvhd AT komalpreetsaggu immunometabolictherapeutictargetsofgraftversushostdiseasegvhd AT nataliyaprokopenkobuxbaum immunometabolictherapeutictargetsofgraftversushostdiseasegvhd
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Immunometabolic Therapeutic Targets of Graft-versus-Host Disease (GvHD)

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