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Human skin-resident CD8+T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a
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- Zitti, Beatrice (author)
- Karolinska Inst, Sweden
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- Hoffer, Elena (author)
- Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Univ Copenhagen, Denmark
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- Zheng, Wenning (author)
- Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Univ Copenhagen, Denmark
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- (creator_code:org_t)
- CELL PRESS, 2023
- 2023
- English.
- In: Immunity. - : CELL PRESS. - 1074-7613 .- 1097-4180. ; 56:6, s. 1285-1302.e7
- Journal article (peer-reviewed)
Abstract
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- The integrin CD49a marks highly cytotoxic epidermal-tissue-resident memory (TRM) cells, but their differen-tiation from circulating populations remains poorly defined. We demonstrate enrichment of RUNT family tran-scription-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 be-tween 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-b induced CD49a expres-sion and cytotoxic transcriptional profiles in a RUNX2-and RUNX3-dependent manner. We therefore identi-fied 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 pa-tient survival. Together, our results indicate that combined RUNX2 and RUNX3 activity promotes the differ-entiation of cytotoxic CD8+CD103+CD49a+ TRM cells, providing immunosurveillance of infected and malig-nant cells.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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- Linköping University
- Karolinska Institutet
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