Details

Autor(en) / Beteiligte

• 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
• Murphy, George F.
• Kupper, Thomas S.
• Frank, Natasha Y.
• Frank, Markus H.

Titel

ABCB5 Identifies Immunoregulatory Dermal Cells

Ist Teil von

• Cell reports (Cambridge), 2015-09, Vol.12 (10), p.1564-1574

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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. [Display omitted] •Mammalian skin contains dermal immunoregulatory cells (DIRCs)•ABCB5 surface expression constitutes a molecular marker for the isolation of DIRCs•DIRCs suppress alloimmunity and prolong cardiac allograft survival•Efficient DIRC-mediated immunosuppression requires PD-1-mediated Treg induction Schatton et al. identify ABCB5 as a marker of dermal cells in mammalian skin that possess immunoregulatory functions, through engagement of the immune checkpoint molecule PD-1. ABCB5-positive cells, when administered to recipients of heart transplants in preclinical models, prolong graft survival, suggesting promising roles of this cell subset in cellular immunotherapy.