Abstract

T cells are important in the pathogenesis of acute kidney injury (AKI), and TCR+CD4-CD8- (double negative-DN) are T cells that have regulatory properties. However, there is limited information on DN T cells compared to traditional CD4+ and CD8+ cells. To elucidate the molecular signature and spatial dynamics of DN T cells during AKI, we performed single-cell RNA sequencing (scRNA-seq) on sorted murine DN, CD4+, and CD8+ cells combined with spatial transcriptomic profiling of normal and post AKI mouse kidneys. scRNA-seq revealed distinct transcriptional profiles for DN, CD4+, and CD8+ T cells of mouse kidneys with enrichment of Kcnq5, Klrb1c, Fcer1g, and Klre1 expression in DN T cells compared to CD4+ and CD8+ T cells in normal kidney tissue. We validated the expression of these four genes in mouse kidney DN, CD4+ and CD8+ T cells using RT-PCR and Kcnq5, Klrb1, and Fcer1g genes with the NIH human kidney precision medicine project (KPMP). Spatial transcriptomics in normal and ischemic mouse kidney tissue showed a localized cluster of T cells in the outer medulla expressing DN T cell genes including Fcer1g. These results provide a template for future studies in DN T as well as CD4+ and CD8+ cells in normal and diseased kidneys.

Details

Title
Single cell and spatial transcriptomics analysis of kidney double negative T lymphocytes in normal and ischemic mouse kidneys
Author
Gharaie, Sepideh 1 ; Lee, Kyungho 1 ; Noller, Kathleen 2 ; Lo, Emily K. 2 ; Miller, Brendan 2 ; Jung, Hyun Jun 1 ; Newman-Rivera, Andrea M. 1 ; Kurzhagen, Johanna T. 1 ; Singla, Nirmish 3 ; Welling, Paul A. 4 ; Fan, Jean 2 ; Cahan, Patrick 2 ; Noel, Sanjeev 1 ; Rabb, Hamid 1 

 Johns Hopkins University, School of Medicine, Department of Medicine, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
 Johns Hopkins University, School of Medicine, Department of Biomedical Engineering, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
 Johns Hopkins University, School of Medicine, Department of Urology, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
 Johns Hopkins University, School of Medicine, Department of Medicine, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311); Johns Hopkins University, School of Medicine, Department of Physiology, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
Pages
20888
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2894594074
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.