Schatton T; Yang J; Kleffel S; Uehara M; Barthel SR; Schlapbach C; Zhan Q; Dudeney S; Mueller H; Lee N; de Vries JC; Meier B; Vander Beken S; Kluth MA; Ganss C; Sharpe AH; Waaga-Gasser AM; Sayegh MH; Abdi R; Scharffetter-Kochanek K; Murphy GF; Kupper TS; Frank NY; Frank MH
Cell Rep 2015[Sep]; 12 (10): 1564-74 PMID26321644show ga
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 MHC-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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Cell+Rep 2015 ; 12 (10): 1564-74
