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| Status |
Public on Mar 01, 2024 |
| Title |
Cognate antigen-independent differentiation of resident memory t cells in chronic kidney disease |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Although resident memory T cells (TRMs), which are memory T cells that are retained locally within tissues, have recently been described as antigen-specific frontline defenders against pathogens in barrier and non-barrier epithelial tissues, they have also been noted for perpetuating chronic inflammation. Furthermore, the conditions responsible for TRM differentiation are still poorly understood, and their contributions, if any, to sterile models of chronic kidney disease (CKD) remain a mystery. In this study we identify a substantial population of TRMs in the kidneys of mice with aristolochic acid (AA)-induced CKD. Flow cytometry of injured kidneys showed T cells bearing TRM surface markers and single cell RNA sequencing revealed these cells as expressing well-known TRM transcription factors and receptors responsible for TRM differentiation and maintenance. While kidney TRMs expressed Cd44, a marker of antigen experience and T cell activation, their derivation was surprisingly independent of cognate antigen-T cell receptor interactions, as the kidneys of transgenic OT-1 mice still harbored considerable proportions of TRMs after injury. Our results suggest a non-antigen-specific or antigen-independent mechanism capable of generating TRMs in the kidney and highlight the need to better understand TRMs and their involvement in CKD.
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| Overall design |
C57BL/6J mice were administered aristolochic acid 2 mg/kg body weight i.p. for 5 consecutive days and kidneys were harvested two and six weeks later for single cell RNA sequencing. Quiescent kidney immune cell sequencing from GSE200115 was used for controls.
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| Web link |
https://doi.org/10.6084/m9.figshare.24600063.v1
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| Contributor(s) |
Moore KH, Erman EN, Traylor AM, Esman SK, Jiang Y, LaFontaine JR, Zmijewska A, Lu Y, Soliman RH, George JF, Agarwal A |
| Citation(s) |
38450434 |
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| Submission date |
Nov 01, 2023 |
| Last update date |
Mar 07, 2024 |
| Contact name |
Kyle Hartley Moore |
| E-mail(s) |
kylemoore@uabmc.edu
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| Organization name |
University of Alabama at Birmingham
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| Department |
Division of Nephrology
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| Lab |
Anupam Agarwal
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| Street address |
703 19th St. S.
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| City |
Birmingham |
| State/province |
Alabama |
| ZIP/Postal code |
35294 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1034630 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE246803_HTO_details_README.txt |
265 b |
(ftp)(http) |
TXT |
| GSE246803_RAW.tar |
160.7 Mb |
(http)(custom) |
TAR (of TAR) |
SRA Run Selector |
| Raw data are available in SRA |
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