ABCB5 Identifies Immunoregulatory Dermal Cells

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; ... (2015). ABCB5 Identifies Immunoregulatory Dermal Cells. Cell reports, 12(10), pp. 1564-1574. Cell Press 10.1016/j.celrep.2015.08.010

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology

UniBE Contributor:

Schlapbach, Christoph

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2211-1247

Publisher:

Cell Press

Language:

English

Submitter:

Sandra Nyffenegger

Date Deposited:

14 Mar 2016 09:15

Last Modified:

15 Mar 2016 11:40

Publisher DOI:

10.1016/j.celrep.2015.08.010

PubMed ID:

26321644

BORIS DOI:

10.7892/boris.76585

URI:

https://boris.unibe.ch/id/eprint/76585

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