| Autor: |
Freuchet, Antoine, Roy, Payel, Armstrong, Sujit Silas, Oliaeimotlagh, Mohammad, Kumar, Sunil, Orecchioni, Marco, Ali, Amal J., Khan, Amir, Makings, Jeffrey, Lyu, Qingkang, Winkels, Holger, Wang, Erpei, Durant, Christopher, Ghosheh, Yanal, Gulati, Rishab, Nettersheim, Felix, Ley, Klaus |
| Zdroj: |
Nature Immunology; October 2023, Vol. 24 Issue: 10 p1748-1761, 14p |
| Abstrakt: |
In atherosclerosis, some regulatory T (Treg) cells become exTregcells. We crossed inducible Tregand exTregcell lineage-tracker mice (FoxP3eGFP−Cre-ERT2ROSA26CAG-fl-stop-fl-tdTomato) to atherosclerosis-prone Apoe−/−mice, sorted Tregcells and exTregcells and determined their transcriptomes by bulk RNA sequencing (RNA-seq). Genes that were differentially expressed between mouse Tregcells and exTregcells and filtered for their presence in a human single-cell RNA-sequencing (scRNA-seq) panel identified exTregcell signature genes as CST7, NKG7, GZMA, PRF1, TBX21and CCL4. Projecting these genes onto the human scRNA-seq with CITE-seq data identified human exTregcells as CD3+CD4+CD16+CD56+, which was validated by flow cytometry. Bulk RNA-seq of sorted human exTregcells identified them as inflammatory and cytotoxic CD4+T cells that were significantly distinct from both natural killer and Tregcells. DNA sequencing for T cell receptor-β showed clonal expansion of Tregcell CDR3 sequences in exTregcells. Cytotoxicity was functionally demonstrated in cell killing and CD107a degranulation assays, which identifies human exTregcells as cytotoxic CD4+T cells. |
| Databáze: |
Supplemental Index |
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