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

Cell Stem Cell. 2018 Mar 1;22(3):445-453.e5. doi: 10.1016/j.stem.2018.01.017. Epub 2018 Feb 15.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism*
  • Animals
  • Bone Marrow Cells / metabolism*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / immunology*
  • Mice, Inbred C57BL
  • Oxidative Stress
  • Signaling Lymphocytic Activation Molecule Family Member 1 / metabolism*
  • Stem Cell Niche
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • Slamf1 protein, mouse
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • Adenosine