ABCB5 Identifies Immunoregulatory Dermal Cells

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 der...

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Published in:	Cell reports (Cambridge) Vol. 12; no. 10; pp. 1564 - 1574
Main Authors:	Schatton, Tobias, Yang, Jun, Kleffel, Sonja, Uehara, Mayuko, Barthel, Steven R., Schlapbach, Christoph, Zhan, Qian, Dudeney, Stephen, Mueller, Hansgeorg, Lee, Nayoung, de Vries, Juliane C., Meier, Barbara, Vander Beken, Seppe, Kluth, Mark A., Ganss, Christoph, Sharpe, Arlene H., Waaga-Gasser, Ana Maria, Sayegh, Mohamed H., Abdi, Reza, Scharffetter-Kochanek, Karin, Murphy, George F., Kupper, Thomas S., Frank, Natasha Y., Frank, Markus H.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 08-09-2015 Elsevier
Subjects:	Allografts Animals ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Biomarkers - metabolism Cell Proliferation Cells, Cultured Dermis - cytology Graft Survival Heart Transplantation Humans Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout Programmed Cell Death 1 Receptor - genetics Programmed Cell Death 1 Receptor - metabolism T-Lymphocytes - immunology T-Lymphocytes, Regulatory - physiology
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Summary:	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. [Display omitted] •Mammalian skin contains dermal immunoregulatory cells (DIRCs)•ABCB5 surface expression constitutes a molecular marker for the isolation of DIRCs•DIRCs suppress alloimmunity and prolong cardiac allograft survival•Efficient DIRC-mediated immunosuppression requires PD-1-mediated Treg induction 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2015.08.010