CD150 Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege Via Adenosine

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Feb 20

PMID 29456159

Citations 142

Authors

Yuichi Hirata

Kazuhiro Furuhashi

Hiroshi Ishii

Hao Wei Li

Sandra Pinho

Lei Ding

Simon C Robson

Paul S Frenette

Joji Fujisaki

Affiliations

Soon will be listed here.

Abstract

A crucial player in immune regulation, FoxP3 regulatory T cells (Tregs) are drawing attention for their heterogeneity and noncanonical functions. Here, we describe a Treg subpopulation that controls hematopoietic stem cell (HSC) quiescence and engraftment. These Tregs highly expressed an HSC marker, CD150, and localized within the HSC niche in the bone marrow (BM). Specific reduction of BM Tregs achieved by conditional deletion of CXCR4 in Tregs increased HSC numbers in the BM. Adenosine generated via the CD39 cell surface ectoenzyme on niche Tregs protected HSCs from oxidative stress and maintained HSC quiescence. In transplantation settings, niche Tregs prevented allogeneic (allo-) HSC rejection through adenosine and facilitated allo-HSC engraftment. Furthermore, transfer of niche Tregs promoted allo-HSC engraftment to a much greater extent than transfer of other Tregs. These results identify a unique niche-associated Treg subset and adenosine as regulators of HSC quiescence, abundance, and engraftment, further highlighting their therapeutic utility.

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