Translational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease

Graft versus host disease (GVHD) is the major non-relapse complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). Unfortunately, GVHD occurs in roughly half of patients following this therapy and can induce severe life-threatening side effects and premature mortality....

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Autores principales:	Aditya Rayasam, William R. Drobyski
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	graft versus host disease inflammatory cytokines gastrointestinal tract translational clinical trials allogeneic hematopoietic stem cell transplantation mouse models Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/a102fdc62b844ae9b9c5a472aef56059
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spelling	oai:doaj.org-article:a102fdc62b844ae9b9c5a472aef560592021-12-01T08:22:27ZTranslational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease1664-322410.3389/fimmu.2021.779076https://doaj.org/article/a102fdc62b844ae9b9c5a472aef560592021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.779076/fullhttps://doaj.org/toc/1664-3224Graft versus host disease (GVHD) is the major non-relapse complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). Unfortunately, GVHD occurs in roughly half of patients following this therapy and can induce severe life-threatening side effects and premature mortality. The pathophysiology of GVHD is driven by alloreactive donor T cells that induce a proinflammatory environment to cause pathological damage in the skin, gastrointestinal (GI) tract, lung, and liver during the acute phase of this disease. Recent work has demonstrated that the GI tract is a pivotal target organ and a primary driver of morbidity and mortality in patients. Prevention of this complication has therefore emerged as an important goal of prophylaxis strategies given the primacy of this tissue site in GVHD pathophysiology. In this review, we summarize foundational pre-clinical studies that have been conducted in animal models to prevent GI tract GVHD and examine the efficacy of these approaches upon subsequent translation into the clinic. Specifically, we focus on therapies designed to block inflammatory cytokine pathways, inhibit cellular trafficking of alloreactive donor T cells to the GI tract, and reconstitute impaired regulatory networks for the prevention of GVHD in the GI tract.Aditya RayasamWilliam R. DrobyskiWilliam R. DrobyskiFrontiers Media S.A.articlegraft versus host diseaseinflammatory cytokinesgastrointestinal tracttranslational clinical trialsallogeneic hematopoietic stem cell transplantationmouse modelsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	graft versus host disease inflammatory cytokines gastrointestinal tract translational clinical trials allogeneic hematopoietic stem cell transplantation mouse models Immunologic diseases. Allergy RC581-607
spellingShingle	graft versus host disease inflammatory cytokines gastrointestinal tract translational clinical trials allogeneic hematopoietic stem cell transplantation mouse models Immunologic diseases. Allergy RC581-607 Aditya Rayasam William R. Drobyski William R. Drobyski Translational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease
description	Graft versus host disease (GVHD) is the major non-relapse complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). Unfortunately, GVHD occurs in roughly half of patients following this therapy and can induce severe life-threatening side effects and premature mortality. The pathophysiology of GVHD is driven by alloreactive donor T cells that induce a proinflammatory environment to cause pathological damage in the skin, gastrointestinal (GI) tract, lung, and liver during the acute phase of this disease. Recent work has demonstrated that the GI tract is a pivotal target organ and a primary driver of morbidity and mortality in patients. Prevention of this complication has therefore emerged as an important goal of prophylaxis strategies given the primacy of this tissue site in GVHD pathophysiology. In this review, we summarize foundational pre-clinical studies that have been conducted in animal models to prevent GI tract GVHD and examine the efficacy of these approaches upon subsequent translation into the clinic. Specifically, we focus on therapies designed to block inflammatory cytokine pathways, inhibit cellular trafficking of alloreactive donor T cells to the GI tract, and reconstitute impaired regulatory networks for the prevention of GVHD in the GI tract.
format	article
author	Aditya Rayasam William R. Drobyski William R. Drobyski
author_facet	Aditya Rayasam William R. Drobyski William R. Drobyski
author_sort	Aditya Rayasam
title	Translational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease
title_short	Translational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease
title_full	Translational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease
title_fullStr	Translational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease
title_full_unstemmed	Translational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease
title_sort	translational clinical strategies for the prevention of gastrointestinal tract graft versus host disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a102fdc62b844ae9b9c5a472aef56059
work_keys_str_mv	AT adityarayasam translationalclinicalstrategiesforthepreventionofgastrointestinaltractgraftversushostdisease AT williamrdrobyski translationalclinicalstrategiesforthepreventionofgastrointestinaltractgraftversushostdisease AT williamrdrobyski translationalclinicalstrategiesforthepreventionofgastrointestinaltractgraftversushostdisease
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Translational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease

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