GEO series
NKG2D blockade impairs cytotoxic CD8+ tissue resident memory T cell accumulation and attenuates severity of chronic lung allograft dysfunction after transplantation
GSE285515
Homo sapiens
Other; Expression profiling by high throughput sequencing
15 samples
Submitted 2024/12/29
Platform GPL16791
Summary
Chronic lung allograft dysfunction (CLAD) significantly limits long-term survival following lung transplantation. To identify potential targets for CLAD prevention, T cells from explanted CLAD lungs and lung-draining lymph nodes, as well as diseased and non-diseased controls were isolated and single-cell RNA sequencing and TCR sequencing were performed. TCR sequencing revealed a clonally expanded population of tissue resident memory (TRM) CD8+ T cells with high cytotoxic potential including upregulation KLRK1, encoding the co-receptor NKG2D. These cytotoxic CD8+ TRM accumulated around the CLAD airways and had 100-fold increase in clonal overlap with lung draining lymph nodes when compared to non-CLAD lungs. Using a murine model of orthotopic lung transplant, we confirmed that cytotoxic CD8+ TRM accumulation was due to chronic rejection and not transplant alone. Furthermore, blocking NKG2D in-vivo attenuated the airway remodeling following transplantation and diminished airway accumulation of CD8+ T cells. Our findings support NKG2D as a potential therapeutic target for CLAD, affecting cytotoxic CD8+ TRM accumulation.
Published in
Moghbeli K, Lipp MA, Bueno M et al.
· JCI insight 2025
· PMID 39989456
· doi:10.1172/jci.insight.184048
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE285515_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 15 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1204132 and SRA study SRP554320. Searching any of these in the dataset finder brings you back here.
Study design
15 conditions, each sampled once — no replicated groups
Read from 15 sample titles: 15 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
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- GSM8703717 Multiplexed Lungs 1, T-cells, HTO
- GSM8703718 Multiplexed Lungs 1, T-cells, GEX
- GSM8703719 Multiplexed Lungs 1, T-cells, TCR
- GSM8703720 Multiplexed Hilar Lymph Nodes 1, T-cells, HTO
- GSM8703721 Multiplexed Hilar Lymph Nodes 1, T-cells, GEX
- GSM8703722 Multiplexed Hilar Lymph Nodes 1, T-cells, TCR
- GSM8703723 Multiplexed Lungs and Hilar Lymph Nodes 1, T-cells, HTO
- GSM8703724 Multiplexed Lungs and Hilar Lymph Nodes 1, T-cells, GEX
- GSM8703725 Multiplexed Lungs and Hilar Lymph Nodes 1, T-cells, TCR
- GSM8703726 Multiplexed Lungs 2, T-cells, HTO
- GSM8703727 Multiplexed Lungs 2, T-cells, GEX
- GSM8703728 Multiplexed Lungs 2, T-cells, TCR
- GSM8703729 Multiplexed Hilar Lymph Nodes 2, T-cells, HTO
- GSM8703730 Multiplexed Hilar Lymph Nodes 2, T-cells, GEX
- GSM8703731 Multiplexed Hilar Lymph Nodes 2, T-cells, TCR
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