P132 Dextran Sulfate Sodium-Induced Colitis Is Attenuated in Trace Amine Associated Receptor 1 Knockout Mice

Gwilt, Katlynn Bugda; Olliffe, Neva; Hoffing, Rachel; Westmoreland, Susan V.; Schueler, Alexandra; Miller, Gregory M.

doi:10.1093/ibd/izy393.150

Cited by 3 publications

(2 citation statements)

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“…Lactobacillus species, a commensal microbe, showed association with GVHD, produce tyramine, a trace amine and a ligand for TAAR1. (Reikvam et al, 2017;Gwilt et al, 2019) 16 Nitric oxide synthase (NOS) Inhibition NO production has proinflammatory functions like apoptosis in intestinal epithelial cells, killing of alveolar type II epithelial cells, mediating expression of the chemokine macrophage inflammatory Protein-2 (MIP-2) and encourage the immune cells migration with increased NO production. (Vallance and Leiper, 2002) 17 GSH/GSSG dysregulation Regulation The early oxidation of plasma glutathione and its oxidized form (GSH/GSSG) redox couple along with significant increase in hepatic protein oxidative damage and ROS production has been observed irrespective of radiation conditioning treatment.…”

Section: Inhibitionmentioning

confidence: 99%

Metabolic Reprogramming—A New Era How to Prevent and Treat Graft Versus Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation Has Begun

Kumari

Palaniyandi

2020

Front. Pharmacol.

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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.

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