Document Type

Journal Article

Publisher

Elsevier

Faculty

Health, Engineering and Science

School

School of Medical Sciences

RAS ID

19858

Comments

This article was originally published as: Schatton, T., Yang, J., Kleffel, S., Uehara, M., Barthel, S. R., Schlapbach, C., ... & Frank, M. H. (2015). ABCB5 Identifies Immunoregulatory Dermal Cells. Cell reports, 12(10), 1564-1574. Original article available here

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. 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.

DOI

10.1016/j.celrep.2015.08.010

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.