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

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Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a. / Zitti, Beatrice; Hoffer, Elena; Zheng, Wenning; Pandey, Ram Vinay; Schlums, Heinrich; Perinetti Casoni, Giovanna; Fusi, Irene; Nguyen, Lien; Kärner, Jaanika; Kokkinou, Efthymia; Carrasco, Anna; Gahm, Jessica; Ehrström, Marcus; Happaniemi, Staffan; Keita, Åsa V.; Hedin, Charlotte R.H.; Mjösberg, Jenny; Eidsmo, Liv; Bryceson, Yenan T.

In: Immunity, Vol. 56, No. 6, 2023, p. 1285-1302.e7.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zitti, B, Hoffer, E, Zheng, W, Pandey, RV, Schlums, H, Perinetti Casoni, G, Fusi, I, Nguyen, L, Kärner, J, Kokkinou, E, Carrasco, A, Gahm, J, Ehrström, M, Happaniemi, S, Keita, ÅV, Hedin, CRH, Mjösberg, J, Eidsmo, L & Bryceson, YT 2023, 'Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a', Immunity, vol. 56, no. 6, pp. 1285-1302.e7. https://doi.org/10.1016/j.immuni.2023.05.003

APA

Zitti, B., Hoffer, E., Zheng, W., Pandey, R. V., Schlums, H., Perinetti Casoni, G., Fusi, I., Nguyen, L., Kärner, J., Kokkinou, E., Carrasco, A., Gahm, J., Ehrström, M., Happaniemi, S., Keita, Å. V., Hedin, C. R. H., Mjösberg, J., Eidsmo, L., & Bryceson, Y. T. (2023). Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a. Immunity, 56(6), 1285-1302.e7. https://doi.org/10.1016/j.immuni.2023.05.003

Vancouver

Zitti B, Hoffer E, Zheng W, Pandey RV, Schlums H, Perinetti Casoni G et al. Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a. Immunity. 2023;56(6):1285-1302.e7. https://doi.org/10.1016/j.immuni.2023.05.003

Author

Zitti, Beatrice ; Hoffer, Elena ; Zheng, Wenning ; Pandey, Ram Vinay ; Schlums, Heinrich ; Perinetti Casoni, Giovanna ; Fusi, Irene ; Nguyen, Lien ; Kärner, Jaanika ; Kokkinou, Efthymia ; Carrasco, Anna ; Gahm, Jessica ; Ehrström, Marcus ; Happaniemi, Staffan ; Keita, Åsa V. ; Hedin, Charlotte R.H. ; Mjösberg, Jenny ; Eidsmo, Liv ; Bryceson, Yenan T. / Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a. In: Immunity. 2023 ; Vol. 56, No. 6. pp. 1285-1302.e7.

Bibtex

@article{517258e9a5a94769a5a1066b1c104777,
title = "Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a",
abstract = "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.",
keywords = "adaptive immunity, CD69, cytotoxicity, differentiation, epigenetic, integrin αβ, melanoma, skin, tissue-resident memory cells",
author = "Beatrice Zitti and Elena Hoffer and Wenning Zheng and Pandey, {Ram Vinay} and Heinrich Schlums and {Perinetti Casoni}, Giovanna and Irene Fusi and Lien Nguyen and Jaanika K{\"a}rner and Efthymia Kokkinou and Anna Carrasco and Jessica Gahm and Marcus Ehrstr{\"o}m and Staffan Happaniemi and Keita, {{\AA}sa V.} and Hedin, {Charlotte R.H.} and Jenny Mj{\"o}sberg and Liv Eidsmo and Bryceson, {Yenan T.}",
note = "Publisher Copyright: {\textcopyright} 2023",
year = "2023",
doi = "10.1016/j.immuni.2023.05.003",
language = "English",
volume = "56",
pages = "1285--1302.e7",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a

AU - Zitti, Beatrice

AU - Hoffer, Elena

AU - Zheng, Wenning

AU - Pandey, Ram Vinay

AU - Schlums, Heinrich

AU - Perinetti Casoni, Giovanna

AU - Fusi, Irene

AU - Nguyen, Lien

AU - Kärner, Jaanika

AU - Kokkinou, Efthymia

AU - Carrasco, Anna

AU - Gahm, Jessica

AU - Ehrström, Marcus

AU - Happaniemi, Staffan

AU - Keita, Åsa V.

AU - Hedin, Charlotte R.H.

AU - Mjösberg, Jenny

AU - Eidsmo, Liv

AU - Bryceson, Yenan T.

N1 - Publisher Copyright: © 2023

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - adaptive immunity

KW - CD69

KW - cytotoxicity

KW - differentiation

KW - epigenetic

KW - integrin αβ

KW - melanoma

KW - skin

KW - tissue-resident memory cells

U2 - 10.1016/j.immuni.2023.05.003

DO - 10.1016/j.immuni.2023.05.003

M3 - Journal article

C2 - 37269830

AN - SCOPUS:85161292627

VL - 56

SP - 1285-1302.e7

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 6

ER -

ID: 357057271