ABCB5 Identifies Immunoregulatory Dermal Cells

Cell Reports
Tobias SchattonMarkus H Frank

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.

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Citations

Feb 2, 2016·The Journal of Investigative Dermatology·Sonja KleffelTobias Schatton
Jun 15, 2016·Stem Cells·Dongsheng JiangKarin Scharffetter-Kochanek
Sep 18, 2016·The Journal of Investigative Dermatology·Zhe JianXiao-Jing Wang
Dec 27, 2016·The Journal of Investigative Dermatology·Rubén A FerrerSandra Franz
Oct 28, 2017·Journal of Translational Medicine·Jeong-Hee Yang, Seok-Chan Eun
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May 10, 2019·Tissue Engineering. Part B, Reviews·Mustafa Hussain KathawalaKee Woei Ng
Jul 28, 2019·Experimental Dermatology·Shadi KhalilArturo P Saavedra
Oct 28, 2019·Stem Cells Translational Medicine·Åsa Ekblad-NordbergCecilia Götherström
Mar 18, 2020·Expert Opinion on Biological Therapy·Allison R KeithJakub Tolar
Aug 23, 2019·Archives of Toxicology·Vanessa HartwigSteven Dooley
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Apr 5, 2020·The American Journal of Pathology·Eleanor Russell-Goldman, George F Murphy

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