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Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry

Diabetic nephropathy (DN) is the most prominent cause of chronic kidney disease and end-stage renal failure. However, the pathophysiology of DN, especially the risk factors for early onset remains elusive. Increasing evidence has revealed the role of the innate immune system in developing DN, but re...

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Autores principales: Jin, Juan, Wang, Longqiang, Liu, Yongjun, He, Wenfang, Zheng, Danna, Ni, Yinhua, He, Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853014/
https://www.ncbi.nlm.nih.gov/pubmed/36686486
http://dx.doi.org/10.3389/fendo.2022.1018608
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author Jin, Juan
Wang, Longqiang
Liu, Yongjun
He, Wenfang
Zheng, Danna
Ni, Yinhua
He, Qiang
author_facet Jin, Juan
Wang, Longqiang
Liu, Yongjun
He, Wenfang
Zheng, Danna
Ni, Yinhua
He, Qiang
author_sort Jin, Juan
collection PubMed
description Diabetic nephropathy (DN) is the most prominent cause of chronic kidney disease and end-stage renal failure. However, the pathophysiology of DN, especially the risk factors for early onset remains elusive. Increasing evidence has revealed the role of the innate immune system in developing DN, but relatively little is known about early immunological change that proceeds from overt DN. Herein, this work aims to investigate the immune-driven pathogenesis of DN using mass cytometry (CyTOF). The peripheral blood mononuclear lymphocytes (PBMC) from 6 patients with early-stage nephropathy and 7 type II diabetes patients without nephropathy were employed in the CyTOF test. A panel that contains 38 lineage markers was designed to monitor immune protein levels in PBMC. The unsupervised clustering analysis was performed to profile the proportion of individual cells. t-Distributed Stochastic Neighbor Embedding (t-SNE) was used to visualize the differences in DN patients’ immune phenotypes. Comprehensive immune profiling revealed substantial immune system alterations in the early onset of DN, including the significant decline of B cells and the marked increase of monocytes. The level of CXCR3 was dramatically reduced in the different immune cellular subsets. The CyTOF data classified the fine-grained differential immune cell subsets in the early stage of DN. Innovatively, we identified several significant changed T cells, B cell, and monocyte subgroups in the early-stage DN associated with several potential biomarkers for developing DN, such as CTLA-4, CXCR3, PD-1, CD39, CCR4, and HLA-DR. Correlation analysis further demonstrated the robust relationship between above immune cell biomarkers and clinical parameters in the DN patients. Therefore, we provided a convincible view of understanding the immune-driven early pathogenesis of DN. Our findings exhibited that patients with DN are more susceptible to immune system disorders. The classification of fine-grained immune cell subsets in this present research might provide novel targets for the immunotherapy of DN.
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spelling pubmed-98530142023-01-21 Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry Jin, Juan Wang, Longqiang Liu, Yongjun He, Wenfang Zheng, Danna Ni, Yinhua He, Qiang Front Endocrinol (Lausanne) Endocrinology Diabetic nephropathy (DN) is the most prominent cause of chronic kidney disease and end-stage renal failure. However, the pathophysiology of DN, especially the risk factors for early onset remains elusive. Increasing evidence has revealed the role of the innate immune system in developing DN, but relatively little is known about early immunological change that proceeds from overt DN. Herein, this work aims to investigate the immune-driven pathogenesis of DN using mass cytometry (CyTOF). The peripheral blood mononuclear lymphocytes (PBMC) from 6 patients with early-stage nephropathy and 7 type II diabetes patients without nephropathy were employed in the CyTOF test. A panel that contains 38 lineage markers was designed to monitor immune protein levels in PBMC. The unsupervised clustering analysis was performed to profile the proportion of individual cells. t-Distributed Stochastic Neighbor Embedding (t-SNE) was used to visualize the differences in DN patients’ immune phenotypes. Comprehensive immune profiling revealed substantial immune system alterations in the early onset of DN, including the significant decline of B cells and the marked increase of monocytes. The level of CXCR3 was dramatically reduced in the different immune cellular subsets. The CyTOF data classified the fine-grained differential immune cell subsets in the early stage of DN. Innovatively, we identified several significant changed T cells, B cell, and monocyte subgroups in the early-stage DN associated with several potential biomarkers for developing DN, such as CTLA-4, CXCR3, PD-1, CD39, CCR4, and HLA-DR. Correlation analysis further demonstrated the robust relationship between above immune cell biomarkers and clinical parameters in the DN patients. Therefore, we provided a convincible view of understanding the immune-driven early pathogenesis of DN. Our findings exhibited that patients with DN are more susceptible to immune system disorders. The classification of fine-grained immune cell subsets in this present research might provide novel targets for the immunotherapy of DN. Frontiers Media S.A. 2023-01-06 /pmc/articles/PMC9853014/ /pubmed/36686486 http://dx.doi.org/10.3389/fendo.2022.1018608 Text en Copyright © 2023 Jin, Wang, Liu, He, Zheng, Ni and He 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 Endocrinology
Jin, Juan
Wang, Longqiang
Liu, Yongjun
He, Wenfang
Zheng, Danna
Ni, Yinhua
He, Qiang
Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry
title Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry
title_full Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry
title_fullStr Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry
title_full_unstemmed Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry
title_short Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry
title_sort depiction of immune heterogeneity of peripheral blood from patients with type ii diabetic nephropathy based on mass cytometry
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853014/
https://www.ncbi.nlm.nih.gov/pubmed/36686486
http://dx.doi.org/10.3389/fendo.2022.1018608
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