ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2021 Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Search

Single Nuclei RNA-Sequencing Identifies Distinct Immune Cell Profile in Kidney Allograft Fibrosis

J. McDaniels1, A. Shetty1, C. Kuscu2, C. Kuscu2, T. Rousselle1, E. Bardhi1, C. Drachenberg1, M. Talwar2, J. Eason2, T. Muthukumar3, D. Maluf1, V. Mas1

1University of Maryland Baltimore, Baltimore, MD, 2UTHSC, Memphis, TN, 3Weill Cornell Medicine, New York, NY

Meeting: 2022 American Transplant Congress

Abstract number: 679

Keywords: Fibrosis, Kidney, Kidney transplantation

Topic: Basic Science » Basic Clinical Science » 19 - Chronic Organ Rejection

Session Information

Session Name: Chronic Organ Rejection

Session Type: Poster Abstract

Date: Saturday, June 4, 2022

Session Time: 5:30pm-7:00pm

 Presentation Time: 5:30pm-7:00pm

Location: Hynes Halls C & D

*Purpose: A major obstacle after kidney transplantation (KT) is chronic allograft dysfunction characterized by interstitial fibrosis and tubular atrophy (IFTA). Despite extensive research, the cellular immune response associated with IFTA is unclear. Single nuclei RNA sequencing (snRNA-seq) is a powerful tool to uncover the immune landscape.

*Methods: snRNA-seq was performed for normal (N=3) and IFTA (N=5) human allografts characterized by Banff classifications (all were functional at ≥15mos posttransplant). Sequences were aligned using CellRanger and integrated using the R package Seurat. Ligand receptor analysis utilized the LRdb and an interaction score was computed using machine learning. XY chromosome linked gene expression analysis was used to determine cellular origins using sex-mismatched KTs.

*Results: Differences in extracellular matrix (ECM) production and immune cells led to the identification of two IFTA groups, high and low ECM. A total of 12 immune cell subclusters were generated including B cells, dendritic cells, mast cells, monocytes, plasma cells, and T cells. Low ECM were abundant in monocytes (MO1/MO2), dendritic cells (conventional and plasmacytoid), and mast cells. High ECM accumulated more T cells (CD8+ T cells, NK cells, and Tregs) and B cells. MO1 and MO2 expressed several pro-inflammatory factors including HLA class II antigens (HLA-DRA, HLA-DPA1, HLA-DQA1). Immune cell chimerism was identified, although predominantly of recipient origin. Gene expression analysis also identified a subcluster of resident macrophages in IFTA kidneys, mediating a novel role in fibrosis and tissue repair. Monocyte paracrine signaling highlighted activation of diverse cellular processes and reciprocal anti- and pro-inflammatory signaling.

*Conclusions: To our knowledge, this is the first time the immune cell landscape is described in human kidneys of chronic injury ≥15mos posttranslantation. These findings show that kidney grafts carry immune cells of both donor- and recipient-origin for many years after KT. The differences in immune cell abundance and specific cell types found in fibrotic kidneys may contribute to the activation of the adaptive versus innate response. Assessment of immune responses and signaling is necessary to uncover the dysfunctional pathways related to kidney graft injury and outcomes.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

To cite this abstract in AMA style:

McDaniels J, Shetty A, Kuscu C, Kuscu C, Rousselle T, Bardhi E, Drachenberg C, Talwar M, Eason J, Muthukumar T, Maluf D, Mas V. Single Nuclei RNA-Sequencing Identifies Distinct Immune Cell Profile in Kidney Allograft Fibrosis [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/single-nuclei-rna-sequencing-identifies-distinct-immune-cell-profile-in-kidney-allograft-fibrosis/. Accessed May 30, 2025.

« Back to 2022 American Transplant Congress

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2025 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences