Single-Cell RNA Sequencing Reveals the Immunological Profiles of Renal Allograft Rejection in Mice

Allograft rejection is a common immunological feature in renal transplantation and is associated with reduced graft survival. A mouse renal allograft rejection model was induced and single-cell RNA sequencing (scRNA-seq) data of CD45+ leukocytes in kidney allografts on days 7 (D7) and 15 (D15) after...

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Main Authors: Qixia Shen, Yucheng Wang, Jiaoyi Chen, Lifeng Ma, Xiaoru Huang, Sydney C. W. Tang, Huiyao Lan, Hong Jiang, Jianghua Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.693608/full
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author Qixia Shen
Qixia Shen
Qixia Shen
Qixia Shen
Yucheng Wang
Yucheng Wang
Yucheng Wang
Jiaoyi Chen
Lifeng Ma
Xiaoru Huang
Xiaoru Huang
Sydney C. W. Tang
Huiyao Lan
Hong Jiang
Hong Jiang
Hong Jiang
Jianghua Chen
Jianghua Chen
Jianghua Chen
author_facet Qixia Shen
Qixia Shen
Qixia Shen
Qixia Shen
Yucheng Wang
Yucheng Wang
Yucheng Wang
Jiaoyi Chen
Lifeng Ma
Xiaoru Huang
Xiaoru Huang
Sydney C. W. Tang
Huiyao Lan
Hong Jiang
Hong Jiang
Hong Jiang
Jianghua Chen
Jianghua Chen
Jianghua Chen
author_sort Qixia Shen
collection DOAJ
description Allograft rejection is a common immunological feature in renal transplantation and is associated with reduced graft survival. A mouse renal allograft rejection model was induced and single-cell RNA sequencing (scRNA-seq) data of CD45+ leukocytes in kidney allografts on days 7 (D7) and 15 (D15) after operation was analyzed to reveal a full immunological profiling. We identified 20 immune cell types among 10,921 leukocytes. Macrophages and CD8+ T cells constituted the main populations on both timepoints. In the process from acute rejection (AR) towards chronic rejection (CR), the proportion of proliferating and naïve CD8+ T cells dropped significantly. Both B cells and neutrophils decreased by about 3 folds. On the contrary, the proportion of macrophages and dendritic cells (DCs) increased significantly, especially by about a 4.5-fold increase in Ly6cloMrc1+ macrophages and 2.6 folds increase in Ly6cloEar2+ macrophages. Moreover, myeloid cells harbored the richest ligand and receptor (LR) pairs with other cells, particularly for chemokine ligands such as Cxcl9, Cxcl10, Cxcl16 and Yars. However, macrophages with weak response to interferon gamma (IFNg) contributed to rejection chronicization. To conclude, reduction in CD8 T cells, B cells and neutrophils while increasing in Ly6cloMrc1+ macrophages and Ly6cloEar2+ macrophages, may contribute significantly to the progress from AR towards CR.
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spelling doaj.art-6340c25fe1354964b3b602a9cc2f778a2022-12-21T22:14:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.693608693608Single-Cell RNA Sequencing Reveals the Immunological Profiles of Renal Allograft Rejection in MiceQixia Shen0Qixia Shen1Qixia Shen2Qixia Shen3Yucheng Wang4Yucheng Wang5Yucheng Wang6Jiaoyi Chen7Lifeng Ma8Xiaoru Huang9Xiaoru Huang10Sydney C. W. Tang11Huiyao Lan12Hong Jiang13Hong Jiang14Hong Jiang15Jianghua Chen16Jianghua Chen17Jianghua Chen18Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephrology, Zhejiang University, Hangzhou, ChinaDepartment of Medicine & Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephrology, Zhejiang University, Hangzhou, ChinaDepartment of Medicine & Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaCenter for Stem Cell and Regenerative Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Medicine & Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaGuangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases, Guangdong Academy of Medical Sciences, Guangdong Provincial People’s Hospital, Guangzhou, ChinaDivision of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong, ChinaDepartment of Medicine & Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephrology, Zhejiang University, Hangzhou, ChinaKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaInstitute of Nephrology, Zhejiang University, Hangzhou, ChinaAllograft rejection is a common immunological feature in renal transplantation and is associated with reduced graft survival. A mouse renal allograft rejection model was induced and single-cell RNA sequencing (scRNA-seq) data of CD45+ leukocytes in kidney allografts on days 7 (D7) and 15 (D15) after operation was analyzed to reveal a full immunological profiling. We identified 20 immune cell types among 10,921 leukocytes. Macrophages and CD8+ T cells constituted the main populations on both timepoints. In the process from acute rejection (AR) towards chronic rejection (CR), the proportion of proliferating and naïve CD8+ T cells dropped significantly. Both B cells and neutrophils decreased by about 3 folds. On the contrary, the proportion of macrophages and dendritic cells (DCs) increased significantly, especially by about a 4.5-fold increase in Ly6cloMrc1+ macrophages and 2.6 folds increase in Ly6cloEar2+ macrophages. Moreover, myeloid cells harbored the richest ligand and receptor (LR) pairs with other cells, particularly for chemokine ligands such as Cxcl9, Cxcl10, Cxcl16 and Yars. However, macrophages with weak response to interferon gamma (IFNg) contributed to rejection chronicization. To conclude, reduction in CD8 T cells, B cells and neutrophils while increasing in Ly6cloMrc1+ macrophages and Ly6cloEar2+ macrophages, may contribute significantly to the progress from AR towards CR.https://www.frontiersin.org/articles/10.3389/fimmu.2021.693608/fullScRNA-seqimmunological profilesrenal transplantationacute rejectionchronic rejection
spellingShingle Qixia Shen
Qixia Shen
Qixia Shen
Qixia Shen
Yucheng Wang
Yucheng Wang
Yucheng Wang
Jiaoyi Chen
Lifeng Ma
Xiaoru Huang
Xiaoru Huang
Sydney C. W. Tang
Huiyao Lan
Hong Jiang
Hong Jiang
Hong Jiang
Jianghua Chen
Jianghua Chen
Jianghua Chen
Single-Cell RNA Sequencing Reveals the Immunological Profiles of Renal Allograft Rejection in Mice
Frontiers in Immunology
ScRNA-seq
immunological profiles
renal transplantation
acute rejection
chronic rejection
title Single-Cell RNA Sequencing Reveals the Immunological Profiles of Renal Allograft Rejection in Mice
title_full Single-Cell RNA Sequencing Reveals the Immunological Profiles of Renal Allograft Rejection in Mice
title_fullStr Single-Cell RNA Sequencing Reveals the Immunological Profiles of Renal Allograft Rejection in Mice
title_full_unstemmed Single-Cell RNA Sequencing Reveals the Immunological Profiles of Renal Allograft Rejection in Mice
title_short Single-Cell RNA Sequencing Reveals the Immunological Profiles of Renal Allograft Rejection in Mice
title_sort single cell rna sequencing reveals the immunological profiles of renal allograft rejection in mice
topic ScRNA-seq
immunological profiles
renal transplantation
acute rejection
chronic rejection
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.693608/full
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