Distinct Regulatory and Effector T Cell Metabolic Demands during Graft-Versus-Host Disease

Keli L. Hippen; Ethan Aguilar; Stephanie Y. Rhee; Sara Bolivar-Wagers; Bruce R. Blazar

doi:10.1016/j.it.2019.11.005

Distinct Regulatory and Effector T Cell Metabolic Demands during Graft-Versus-Host Disease

Keli L. Hippen
, Ethan Aguilar
, Stephanie Y. Rhee
, Sara Bolivar-Wagers
, Bruce R. Blazar

Research output: Contribution to journal › Review article › peer-review

39 Scopus citations

Abstract

Despite graft-versus-host disease (GVHD) prophylactic agents, the success and wider utilization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by GVHD. Increasing donor graft regulatory T cell (Treg):effector T cell (Teff) ratios can substantially reduce GVHD in cancer patients, but pre-HSCT conditioning regimens and GVHD create a challenging inflammatory environment for Treg stability, persistence, and function. Metabolism plays a crucial role in T cell and Treg differentiation, and development of effector function. Although glycolysis is a main driver of allogeneic T cell-driven GVHD, oxidative phosphorylation is a main driver of Treg suppressor function. This review focuses on recent advances in our understanding of Treg metabolism in the context of GVHD, and discusses potential therapeutic applications of Tregs in the prevention or treatment of GVHD in cancer patients.

Original language	English (US)
Pages (from-to)	77-91
Number of pages	15
Journal	Trends in Immunology
Volume	41
Issue number	1
DOIs	https://doi.org/10.1016/j.it.2019.11.005
State	Published - Jan 2020

Bibliographical note

Funding Information:
This work was supported in part by research grants from the Children's Cancer Research Fund (K.L.H.), the Leukemia and Lymphoma Society (translational research grant r6029?07; B.R.B.), the Children's' Cancer Research Fund, the KidsFirst Fund, and the National Institutes of Health (R01 HL11879, P01 AI056299, and National Cancer Institute P01 CA067493; B.R.B.). B.R.B. receives remuneration as an advisor to Kamon Pharmaceuticals, Five Prime Therapeutics, Regeneron Pharmaceuticals, Magenta Therapeutics, and BlueRock Therapeutics; research support from Fate Therapeutics, RXi Pharmaceuticals, Alpine Immune Sciences, Abbvie, and BlueRock Therapeutics; and is a cofounder of Tmunity.

Funding Information:
This work was supported in part by research grants from the Children’s Cancer Research Fund (K.L.H.), the Leukemia and Lymphoma Society (translational research grant r6029–07; B.R.B.), the Children’s' Cancer Research Fund, the KidsFirst Fund , and the National Institutes of Health ( R01 HL11879 , P01 AI056299 , and National Cancer Institute P01 CA067493 ; B.R.B.).

Publisher Copyright:
© 2019 Elsevier Ltd

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Foxp3
GVHD
OXPHOS
Treg
glycolysis
microbiota

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title = "Distinct Regulatory and Effector T Cell Metabolic Demands during Graft-Versus-Host Disease",

abstract = "Despite graft-versus-host disease (GVHD) prophylactic agents, the success and wider utilization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by GVHD. Increasing donor graft regulatory T cell (Treg):effector T cell (Teff) ratios can substantially reduce GVHD in cancer patients, but pre-HSCT conditioning regimens and GVHD create a challenging inflammatory environment for Treg stability, persistence, and function. Metabolism plays a crucial role in T cell and Treg differentiation, and development of effector function. Although glycolysis is a main driver of allogeneic T cell-driven GVHD, oxidative phosphorylation is a main driver of Treg suppressor function. This review focuses on recent advances in our understanding of Treg metabolism in the context of GVHD, and discusses potential therapeutic applications of Tregs in the prevention or treatment of GVHD in cancer patients.",

keywords = "Foxp3, GVHD, OXPHOS, Treg, glycolysis, microbiota",

author = "Hippen, \{Keli L.\} and Ethan Aguilar and Rhee, \{Stephanie Y.\} and Sara Bolivar-Wagers and Blazar, \{Bruce R.\}",

note = "Funding Information: This work was supported in part by research grants from the Children's Cancer Research Fund (K.L.H.), the Leukemia and Lymphoma Society (translational research grant r6029?07; B.R.B.), the Children's' Cancer Research Fund, the KidsFirst Fund, and the National Institutes of Health (R01 HL11879, P01 AI056299, and National Cancer Institute P01 CA067493; B.R.B.). B.R.B. receives remuneration as an advisor to Kamon Pharmaceuticals, Five Prime Therapeutics, Regeneron Pharmaceuticals, Magenta Therapeutics, and BlueRock Therapeutics; research support from Fate Therapeutics, RXi Pharmaceuticals, Alpine Immune Sciences, Abbvie, and BlueRock Therapeutics; and is a cofounder of Tmunity. Funding Information: This work was supported in part by research grants from the Children{\textquoteright}s Cancer Research Fund (K.L.H.), the Leukemia and Lymphoma Society (translational research grant r6029–07; B.R.B.), the Children{\textquoteright}s' Cancer Research Fund, the KidsFirst Fund , and the National Institutes of Health ( R01 HL11879 , P01 AI056299 , and National Cancer Institute P01 CA067493 ; B.R.B.). Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

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AU - Rhee, Stephanie Y.

AU - Bolivar-Wagers, Sara

AU - Blazar, Bruce R.

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N2 - Despite graft-versus-host disease (GVHD) prophylactic agents, the success and wider utilization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by GVHD. Increasing donor graft regulatory T cell (Treg):effector T cell (Teff) ratios can substantially reduce GVHD in cancer patients, but pre-HSCT conditioning regimens and GVHD create a challenging inflammatory environment for Treg stability, persistence, and function. Metabolism plays a crucial role in T cell and Treg differentiation, and development of effector function. Although glycolysis is a main driver of allogeneic T cell-driven GVHD, oxidative phosphorylation is a main driver of Treg suppressor function. This review focuses on recent advances in our understanding of Treg metabolism in the context of GVHD, and discusses potential therapeutic applications of Tregs in the prevention or treatment of GVHD in cancer patients.

AB - Despite graft-versus-host disease (GVHD) prophylactic agents, the success and wider utilization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by GVHD. Increasing donor graft regulatory T cell (Treg):effector T cell (Teff) ratios can substantially reduce GVHD in cancer patients, but pre-HSCT conditioning regimens and GVHD create a challenging inflammatory environment for Treg stability, persistence, and function. Metabolism plays a crucial role in T cell and Treg differentiation, and development of effector function. Although glycolysis is a main driver of allogeneic T cell-driven GVHD, oxidative phosphorylation is a main driver of Treg suppressor function. This review focuses on recent advances in our understanding of Treg metabolism in the context of GVHD, and discusses potential therapeutic applications of Tregs in the prevention or treatment of GVHD in cancer patients.

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KW - GVHD

KW - OXPHOS

KW - Treg

KW - glycolysis

KW - microbiota

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Distinct Regulatory and Effector T Cell Metabolic Demands during Graft-Versus-Host Disease

Abstract

Bibliographical note

UN SDGs

Keywords

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