What question did this study set out to answer?

Investigate the metabolic reprogramming pathways underlying alloreactive T-cell activation before the clinical onset of acute graft-versus-host disease (aGvHD).

March 25, 2022Frontiers in ImmunologyOpen Access

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

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Authors

ZPZengkai PanShanghai Jiao Tong University AHAijie HuangUniversity of Science and Technology of China YHYang HeShanghai Jiao Tong University

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Implication

Transcriptomic cohort analysis reveals glycolytic activation driven by TCR, MYC, and mTORC1 signaling prior to acute GvHD onset, highlighting predictive metabolic biomarkers and therapy targets.

Key Points

Investigate the metabolic reprogramming pathways underlying alloreactive T-cell activation before the clinical onset of acute graft-versus-host disease (aGvHD).
Mined public Gene Expression Omnibus (GEO) datasets to evaluate transcriptional activation across carbohydrate, nucleotide, TCA cycle, and amino acid metabolic pathways in T cells prior to aGvHD onset.
Conducted Pearson correlation analyses between metabolic sub-pathways and immune phenotypes, identified potential master regulators, and formulated a logistic regression predictive model utilizing key glycolytic genes.
Validated the expression of identified glycolytic markers (PFKP, ENO3, GAPDH) and the performance of the predictive risk model in an independent pre-aGvHD patient cohort.
Glycolytic activation displayed the strongest correlation with other metabolic sub-pathways and was positively linked to CD4 memory T-cell activation, proliferation, and migration.
TCR, mTORC1, and MYC signaling pathways, alongside E2F6, were identified as critical transcriptional regulators mediating glycolytic activity in alloreactive T cells.
A predictive risk model constructed with glycolytic genes PFKP, ENO3, and GAPDH demonstrated high discriminative performance and was confirmed by elevated expression of these markers in pre-aGvHD patients.

Cite This Study

Pan et al. (2022) studied this question.

synapsesocial.com/papers/6aa03506982290d0c4348ce0 https://doi.org/10.3389/fimmu.2022.850177

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Implication

Transcriptomic cohort analysis reveals glycolytic activation driven by TCR, MYC, and mTORC1 signaling prior to acute GvHD onset, highlighting predictive metabolic biomarkers and therapy targets.

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

Discussion

Member takes

Implication

Key Points

Cite This Study

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

Discussion

Member takes

Implication

Key Points

Cite This Study

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