PMID- 33343357
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240330
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - Metabolic Reprogramming-A New Era How to Prevent and Treat Graft Versus Host 
      Disease After Allogeneic Hematopoietic Stem Cell Transplantation Has Begun.
PG  - 588449
LID - 10.3389/fphar.2020.588449 [doi]
LID - 588449
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is the solitary 
      therapeutic therapy for many types of hematological cancers. The benefits of this 
      procedure are challenged by graft vs. host disease (GVHD), causing significant 
      morbidity and mortality. Recent advances in the metabolomics field have 
      revolutionized our understanding of complex human diseases, clinical diagnostics 
      and allow to trace the de novo biosynthesis of metabolites. There is growing 
      evidence for metabolomics playing a role in different aspects of GVHD, and 
      therefore metabolomic reprogramming presents a novel tool for this disease. 
      Pre-transplant cytokine profiles and metabolic status of allogeneic transplant 
      recipients is shown to be linked with a threat of acute GVHD. Immune reactions 
      underlying the pathophysiology of GVHD involve higher proliferation and migration 
      of immune cells to the target site, requiring shifts in energy supply and demand. 
      Metabolic changes and reduced availability of oxygen result in tissue and 
      cellular hypoxia which is extensive enough to trigger transcriptional and 
      translational changes. T cells, major players in acute GVHD pathophysiology, show 
      increased glucose uptake and glycolytic activity. Effector T (Teff) cells 
      activated during nutrient limiting conditions in vitro or multiplying during GVHD 
      in vivo, depend more on oxidative phosphorylation (OXPHOS) and fatty acid 
      oxidation (FAO). Dyslipidemia, such as the increase of medium and long chain 
      fatty and polyunsaturated acids in plasma of GVHD patients, has been observed. 
      Sphingolipids associate with inflammatory conditions and cancer. Chronic GVHD 
      (cGVHD) patients show reduced branched-chain amino acids (BCAAs) and increased 
      sulfur-containing metabolites post HSCT. Microbiota-derived metabolites such as 
      aryl hydrocarbon receptor (AhR) ligands, bile acids, plasmalogens and short chain 
      fatty acids vary significantly and affect allogeneic immune responses during 
      acute GVHD. Considering the multitude of possibilities, how altered metabolomics 
      are involved in GVHD biology, multi-timepoints related and multivariable 
      biomarker panels for prognosticating and understanding GVHD are needed. In this 
      review, we will discuss the recent work addressing metabolomics reprogramming to 
      control GVHD in detail.
CI  - Copyright (c) 2020 Kumari, Palaniyandi and Hildebrandt.
FAU - Kumari, Reena
AU  - Kumari R
AD  - Division of Hematology and Blood and Marrow Transplantation, Markey Cancer 
      Center, University of Kentucky, Lexington, KY, United States.
FAU - Palaniyandi, Senthilnathan
AU  - Palaniyandi S
AD  - Division of Hematology and Blood and Marrow Transplantation, Markey Cancer 
      Center, University of Kentucky, Lexington, KY, United States.
FAU - Hildebrandt, Gerhard C
AU  - Hildebrandt GC
AD  - Division of Hematology and Blood and Marrow Transplantation, Markey Cancer 
      Center, University of Kentucky, Lexington, KY, United States.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20201106
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7748087
OTO - NOTNLM
OT  - allogeneic hematopoietic cell transplantation
OT  - glycolysis
OT  - graft versus host disease
OT  - krebs cycle
OT  - t cells
EDAT- 2020/12/22 06:00
MHDA- 2020/12/22 06:01
PMCR- 2020/11/06
CRDT- 2020/12/21 06:04
PHST- 2020/07/28 00:00 [received]
PHST- 2020/09/29 00:00 [accepted]
PHST- 2020/12/21 06:04 [entrez]
PHST- 2020/12/22 06:00 [pubmed]
PHST- 2020/12/22 06:01 [medline]
PHST- 2020/11/06 00:00 [pmc-release]
AID - 588449 [pii]
AID - 10.3389/fphar.2020.588449 [doi]
PST - epublish
SO  - Front Pharmacol. 2020 Nov 6;11:588449. doi: 10.3389/fphar.2020.588449. 
      eCollection 2020.