Schatton, TobiasTobiasSchattonYang, JunJunYangKleffel, SonjaSonjaKleffelUehara, MayukoMayukoUeharaBarthel, Steven RSteven RBarthelSchlapbach, ChristophChristophSchlapbachZhan, QianQianZhanDudeney, StephenStephenDudeneyMueller, HansgeorgHansgeorgMuellerLee, NayoungNayoungLeede Vries, Juliane CJuliane Cde VriesMeier, BarbaraBarbaraMeierVander Beken, SeppeSeppeVander BekenKluth, Mark AMark AKluthGanss, ChristophChristophGanssSharpe, Arlene HArlene HSharpeWaaga-Gasser, Ana MariaAna MariaWaaga-GasserSayegh, Mohamed HMohamed HSayeghAbdi, RezaRezaAbdiScharffetter-Kochanek, KarinKarinScharffetter-KochanekMurphy, George FGeorge FMurphyKupper, Thomas SThomas SKupperFrank, Natasha YNatasha YFrankFrank, Markus HMarkus HFrank2024-10-242024-10-242015-09-08https://boris-portal.unibe.ch/handle/20.500.12422/138523Cell-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.en600 - Technology::610 - Medicine & healtharticle10.7892/boris.765852632164410.1016/j.celrep.2015.08.010