ABCB5 Identifies Immunoregulatory Dermal Cells

Authors

Tobias Schatton
Jun Yang
Sonja Kleffel
Mayuko Uehara
Steven R. Barthel
Christoph Schlapbach
Qian Zhan
Stephen Dudeney
Hansgeorg Mueller
Nayoung Lee
Juliane C. de Vries
Barbara Meier
Seppe Vander Beken
Mark M. Kluth
Christoph Ganss
Arlene H. Sharpe
Ana Maria Waaga-Gasser
Mohamed H. Sayegh
Reza Abdi
Karin Scharffetter-Kochanek
George F. Murphy
Thomas S. Kupper
Natasha Y. Frank
Markus H. Frank, Edith Cowan University

Document Type

Journal Article

Publisher

Elsevier

Faculty

Faculty of Health, Engineering and Science

School

School of Medical Sciences

RAS ID

19858

Comments

Schatton, T., Yang, J., Kleffel, S., Uehara, M., Barthel, S. R., Schlapbach, C., ... & Frank, M. H. (2015). ABCB5 Identifies Immunoregulatory Dermal Cells. Cell reports, 12(10), 1564-1574. Available here

Abstract

Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5+ DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5+ DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy. Schatton et al. identify ABCB5 as a marker of dermal cells in mammalian skin that possess immunoregulatory functions, through engagement of the immune checkpoint molecule PD-1. ABCB5-positive cells, when administered to recipients of heart transplants in preclinical models, prolong graft survival, suggesting promising roles of this cell subset in cellular immunotherapy.

DOI

10.1016/j.celrep.2015.08.010

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