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Metabolic Reprogramming of Alloreactive T Cells Through TCR/MYC/mTORC1/E2F6 Signaling in aGvHD Patients

Acute graft-versus-host disease (aGvHD) is the most common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and significantly linked with morbidity and mortality. Although much work has been engaged to investigate aGvHD pathogenesis, the understanding of alloreactive...

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Autores principales: Pan, Zengkai, Huang, Aijie, He, Yang, Zhang, Zilu, Jiang, Chuanhe, Wang, Luxiang, Qing, Kai, Zhang, Sujiang, Wang, Jianmin, Hu, Xiaoxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989838/
https://www.ncbi.nlm.nih.gov/pubmed/35401560
http://dx.doi.org/10.3389/fimmu.2022.850177
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author Pan, Zengkai
Huang, Aijie
He, Yang
Zhang, Zilu
Jiang, Chuanhe
Wang, Luxiang
Qing, Kai
Zhang, Sujiang
Wang, Jianmin
Hu, Xiaoxia
author_facet Pan, Zengkai
Huang, Aijie
He, Yang
Zhang, Zilu
Jiang, Chuanhe
Wang, Luxiang
Qing, Kai
Zhang, Sujiang
Wang, Jianmin
Hu, Xiaoxia
author_sort Pan, Zengkai
collection PubMed
description Acute graft-versus-host disease (aGvHD) is the most common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and significantly linked with morbidity and mortality. Although much work has been engaged to investigate aGvHD pathogenesis, the understanding of alloreactive T-cell activation remains incomplete. To address this, we studied transcriptional activation of carbohydrate, nucleotide, tricarboxylic acid (TCA) cycle, and amino acid metabolism of T cells before aGvHD onset by mining the Gene Expression Omnibus (GEO) datasets. Glycolysis had the most extensive correlation with other activated metabolic sub-pathways. Through Pearson correlation analyses, we found that glycolytic activation was positively correlated with activated CD4 memory T-cell subset and T-cell proliferation and migration. T-cell receptor (TCR), mechanistic target of rapamycin complex 1 (mTORC1), myelocytomatosis oncogene (MYC) signaling pathways and E2F6 might be “master regulators” of glycolytic activity. aGvHD predictive model constructed by glycolytic genes (PFKP, ENO3, and GAPDH) through logistic regression showed high predictive and discriminative value. Furthermore, higher expressions of PFKP, ENO3, and GAPDH in alloreactive T cells were confirmed in our pre-aGvHD patient cohort. And the predictive value of the aGvHD risk model was also validated. In summary, our study demonstrated that glycolytic activation might play a pivotal function in alloreactive T-cell activation before aGvHD onset and would be the potential target for aGvHD therapy.
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spelling pubmed-89898382022-04-09 Metabolic Reprogramming of Alloreactive T Cells Through TCR/MYC/mTORC1/E2F6 Signaling in aGvHD Patients Pan, Zengkai Huang, Aijie He, Yang Zhang, Zilu Jiang, Chuanhe Wang, Luxiang Qing, Kai Zhang, Sujiang Wang, Jianmin Hu, Xiaoxia Front Immunol Immunology Acute graft-versus-host disease (aGvHD) is the most common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and significantly linked with morbidity and mortality. Although much work has been engaged to investigate aGvHD pathogenesis, the understanding of alloreactive T-cell activation remains incomplete. To address this, we studied transcriptional activation of carbohydrate, nucleotide, tricarboxylic acid (TCA) cycle, and amino acid metabolism of T cells before aGvHD onset by mining the Gene Expression Omnibus (GEO) datasets. Glycolysis had the most extensive correlation with other activated metabolic sub-pathways. Through Pearson correlation analyses, we found that glycolytic activation was positively correlated with activated CD4 memory T-cell subset and T-cell proliferation and migration. T-cell receptor (TCR), mechanistic target of rapamycin complex 1 (mTORC1), myelocytomatosis oncogene (MYC) signaling pathways and E2F6 might be “master regulators” of glycolytic activity. aGvHD predictive model constructed by glycolytic genes (PFKP, ENO3, and GAPDH) through logistic regression showed high predictive and discriminative value. Furthermore, higher expressions of PFKP, ENO3, and GAPDH in alloreactive T cells were confirmed in our pre-aGvHD patient cohort. And the predictive value of the aGvHD risk model was also validated. In summary, our study demonstrated that glycolytic activation might play a pivotal function in alloreactive T-cell activation before aGvHD onset and would be the potential target for aGvHD therapy. Frontiers Media S.A. 2022-03-25 /pmc/articles/PMC8989838/ /pubmed/35401560 http://dx.doi.org/10.3389/fimmu.2022.850177 Text en Copyright © 2022 Pan, Huang, He, Zhang, Jiang, Wang, Qing, Zhang, Wang and Hu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Pan, Zengkai
Huang, Aijie
He, Yang
Zhang, Zilu
Jiang, Chuanhe
Wang, Luxiang
Qing, Kai
Zhang, Sujiang
Wang, Jianmin
Hu, Xiaoxia
Metabolic Reprogramming of Alloreactive T Cells Through TCR/MYC/mTORC1/E2F6 Signaling in aGvHD Patients
title Metabolic Reprogramming of Alloreactive T Cells Through TCR/MYC/mTORC1/E2F6 Signaling in aGvHD Patients
title_full Metabolic Reprogramming of Alloreactive T Cells Through TCR/MYC/mTORC1/E2F6 Signaling in aGvHD Patients
title_fullStr Metabolic Reprogramming of Alloreactive T Cells Through TCR/MYC/mTORC1/E2F6 Signaling in aGvHD Patients
title_full_unstemmed Metabolic Reprogramming of Alloreactive T Cells Through TCR/MYC/mTORC1/E2F6 Signaling in aGvHD Patients
title_short Metabolic Reprogramming of Alloreactive T Cells Through TCR/MYC/mTORC1/E2F6 Signaling in aGvHD Patients
title_sort metabolic reprogramming of alloreactive t cells through tcr/myc/mtorc1/e2f6 signaling in agvhd patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989838/
https://www.ncbi.nlm.nih.gov/pubmed/35401560
http://dx.doi.org/10.3389/fimmu.2022.850177
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