ABCB5 Identifies Immunoregulatory Dermal Cells

作者：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; Beken Seppe Vander; 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^*

来源：Cell Reports, 2015, 12(10): 1564-1574.

DOI：10.1016/j.celrep.2015.08.010

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.

• 出版日期2015-9-8
• 单位华中科技大学