CD150high Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege via Adenosine

Publication date: Available online 15 February 2018
Source:Cell Stem Cell
Author(s): Yuichi Hirata, Kazuhiro Furuhashi, Hiroshi Ishii, Hao Wei Li, Sandra Pinho, Lei Ding, Simon C. Robson, Paul S. Frenette, Joji Fujisaki
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.

Graphical abstract

Teaser

Hirata et al. identify a regulatory T cell (Treg) population that localizes in the hematopoietic stem cell (HSC) niche with high-level expression of CD150, an HSC marker. These niche-associated Tregs maintain HSC quiescence and immune privilege through adenosine. Furthermore, transfer of niche Tregs significantly improves allogeneic HSC engraftment.


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