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T Cells With Activated STAT4 Drive the High-Risk Rejection State to Renal Allograft Failure After Kidney Transplantation

In kidney transplantation, deteriorated progression of rejection is considered to be a leading course of postoperative mortality. However, the conventional histologic diagnosis is limited in reading the rejection status at the molecular level, thereby triggering mismatched pathogenesis with clinical...

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Autores principales: Chen, Yihan, Zhang, Bao, Liu, Tianliang, Chen, Xiaoping, Wang, Yaning, Zhang, Hongbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283858/
https://www.ncbi.nlm.nih.gov/pubmed/35844542
http://dx.doi.org/10.3389/fimmu.2022.895762
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author Chen, Yihan
Zhang, Bao
Liu, Tianliang
Chen, Xiaoping
Wang, Yaning
Zhang, Hongbo
author_facet Chen, Yihan
Zhang, Bao
Liu, Tianliang
Chen, Xiaoping
Wang, Yaning
Zhang, Hongbo
author_sort Chen, Yihan
collection PubMed
description In kidney transplantation, deteriorated progression of rejection is considered to be a leading course of postoperative mortality. However, the conventional histologic diagnosis is limited in reading the rejection status at the molecular level, thereby triggering mismatched pathogenesis with clinical phenotypes. Here, by applying uniform manifold approximation and projection and Leiden algorithms to 2,611 publicly available microarray datasets of renal transplantation, we uncovered six rejection states with corresponding signature genes and revealed a high-risk (HR) state that was essential in promoting allograft loss. By identifying cell populations from single-cell RNA sequencing data that were associated with the six rejection states, we identified a T-cell population to be the pathogenesis-triggering cells associated with the HR rejection state. Additionally, by constructing gene regulatory networks, we identified that activated STAT4, as a core transcription factor that was regulated by PTPN6 in T cells, was closely linked to poor allograft function and prognosis. Taken together, our study provides a novel strategy to help with the precise diagnosis of kidney allograft rejection progression, which is powerful in investigating the underlying molecular pathogenesis, and therefore, for further clinical intervention.
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spelling pubmed-92838582022-07-16 T Cells With Activated STAT4 Drive the High-Risk Rejection State to Renal Allograft Failure After Kidney Transplantation Chen, Yihan Zhang, Bao Liu, Tianliang Chen, Xiaoping Wang, Yaning Zhang, Hongbo Front Immunol Immunology In kidney transplantation, deteriorated progression of rejection is considered to be a leading course of postoperative mortality. However, the conventional histologic diagnosis is limited in reading the rejection status at the molecular level, thereby triggering mismatched pathogenesis with clinical phenotypes. Here, by applying uniform manifold approximation and projection and Leiden algorithms to 2,611 publicly available microarray datasets of renal transplantation, we uncovered six rejection states with corresponding signature genes and revealed a high-risk (HR) state that was essential in promoting allograft loss. By identifying cell populations from single-cell RNA sequencing data that were associated with the six rejection states, we identified a T-cell population to be the pathogenesis-triggering cells associated with the HR rejection state. Additionally, by constructing gene regulatory networks, we identified that activated STAT4, as a core transcription factor that was regulated by PTPN6 in T cells, was closely linked to poor allograft function and prognosis. Taken together, our study provides a novel strategy to help with the precise diagnosis of kidney allograft rejection progression, which is powerful in investigating the underlying molecular pathogenesis, and therefore, for further clinical intervention. Frontiers Media S.A. 2022-07-01 /pmc/articles/PMC9283858/ /pubmed/35844542 http://dx.doi.org/10.3389/fimmu.2022.895762 Text en Copyright © 2022 Chen, Zhang, Liu, Chen, Wang and Zhang 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
Chen, Yihan
Zhang, Bao
Liu, Tianliang
Chen, Xiaoping
Wang, Yaning
Zhang, Hongbo
T Cells With Activated STAT4 Drive the High-Risk Rejection State to Renal Allograft Failure After Kidney Transplantation
title T Cells With Activated STAT4 Drive the High-Risk Rejection State to Renal Allograft Failure After Kidney Transplantation
title_full T Cells With Activated STAT4 Drive the High-Risk Rejection State to Renal Allograft Failure After Kidney Transplantation
title_fullStr T Cells With Activated STAT4 Drive the High-Risk Rejection State to Renal Allograft Failure After Kidney Transplantation
title_full_unstemmed T Cells With Activated STAT4 Drive the High-Risk Rejection State to Renal Allograft Failure After Kidney Transplantation
title_short T Cells With Activated STAT4 Drive the High-Risk Rejection State to Renal Allograft Failure After Kidney Transplantation
title_sort t cells with activated stat4 drive the high-risk rejection state to renal allograft failure after kidney transplantation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283858/
https://www.ncbi.nlm.nih.gov/pubmed/35844542
http://dx.doi.org/10.3389/fimmu.2022.895762
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