Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a
Research output: Contribution to journal › Journal article › Research › peer-review
The integrin CD49a marks highly cytotoxic epidermal-tissue-resident memory (TRM) cells, but their differentiation from circulating populations remains poorly defined. We demonstrate enrichment of RUNT family transcription-factor-binding motifs in human epidermal CD8+CD103+CD49a+ TRM cells, paralleled by high RUNX2 and RUNX3 protein expression. Sequencing of paired skin and blood samples revealed clonal overlap between epidermal CD8+CD103+CD49a+ TRM cells and circulating memory CD8+CD45RA−CD62L+ T cells. In vitro stimulation of circulating CD8+CD45RA−CD62L+ T cells with IL-15 and TGF-β induced CD49a expression and cytotoxic transcriptional profiles in a RUNX2- and RUNX3-dependent manner. We therefore identified a reservoir of circulating cells with cytotoxic TRM potential. In melanoma patients, high RUNX2, but not RUNX3, transcription correlated with a cytotoxic CD8+CD103+CD49a+ TRM cell signature and improved patient survival. Together, our results indicate that combined RUNX2 and RUNX3 activity promotes the differentiation of cytotoxic CD8+CD103+CD49a+ TRM cells, providing immunosurveillance of infected and malignant cells.
Original language | English |
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Journal | Immunity |
Volume | 56 |
Issue number | 6 |
Pages (from-to) | 1285-1302.e7 |
ISSN | 1074-7613 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Publisher Copyright:
© 2023
- adaptive immunity, CD69, cytotoxicity, differentiation, epigenetic, integrin αβ, melanoma, skin, tissue-resident memory cells
Research areas
ID: 357057271