Mus musculus strain:b6
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA644934 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12180049.fastq.gz | Fastqsanger.gz | |||
| SRR12180050.fastq.gz | Fastqsanger.gz | |||
| SRR12180051.fastq.gz | Fastqsanger.gz | |||
| SRR12180052.fastq.gz | Fastqsanger.gz | |||
| SRR12180053.fastq.gz | Fastqsanger.gz |
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Project description:Tissue-resident memory CD8+ T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. While the relevance of Trm in diverse diseases ranging from infection to cancer is appreciated, the development and functional heterogeneity of Trm remain poorly understood. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8+ T cells, including a Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections, and a molecularly distinct Blimp1loId3hi tissue-resident memory population that subsequently accumulated at later infection timepoints. These distinct Trm populations where characterized by unique transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm heterogeneity during infection. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8+ T cell populations with tissue-resident gene-expression signatures within tumors that shared features of terminally-exhausted and progenitor-exhausted T cells, respectively. Clarification of CD8+ T cell ontogeny and heterogeneity in non-lymphoid tissues holds broad implications for enhancing vaccination and immunotherapy approaches.
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