Abstract
Foxp3+ regulatory T cells (Treg cells) modulate the immune system and maintain self-tolerance, but whether they affect haematopoiesis or haematopoietic stem cell (HSC)-mediated reconstitution after transplantation is unclear. Here we show that B-cell lymphopoiesis is impaired in Treg-depleted mice, yet this reduced B-cell lymphopoiesis is rescued by adoptive transfer of affected HSCs or bone marrow cells into Treg-competent recipients. B-cell reconstitution is abrogated in both syngeneic and allogeneic transplantation using Treg-depleted mice as recipients. Treg cells can control physiological IL-7 production that is indispensable for normal B-cell lymphopoiesis and is mainly sustained by a subpopulation of ICAM1+ perivascular stromal cells. Our study demonstrates that Treg cells are important for B-cell differentiation from HSCs by maintaining immunological homoeostasis in the bone marrow microenvironment, both in physiological conditions and after bone marrow transplantation.
Highlights
Foxp[3] þ regulatory T cells (Treg cells) modulate the immune system and maintain self-tolerance, but whether they affect haematopoiesis or haematopoietic stem cell (HSC)-mediated reconstitution after transplantation is unclear
We find that the perivascular ICAM1 þ CD31 À CD45 À TER119 À stromal cells located in the bone marrow (BM) have reduced Interleukin-7 (IL-7) and CXCL12 production after Treg depletion suggesting that activated T cells that are generated in the absence of Treg cells may target lineage-specific BM niche cells, resulting in defective lymphopoiesis from HSC
We show that Treg cells are required to maintain BM stromal cell function and that these cells are necessary for immune reconstitution after transplantation
Summary
Foxp[3] þ regulatory T cells (Treg cells) modulate the immune system and maintain self-tolerance, but whether they affect haematopoiesis or haematopoietic stem cell (HSC)-mediated reconstitution after transplantation is unclear. We find that the perivascular ICAM1 þ CD31 À CD45 À TER119 À stromal cells located in the BM have reduced Interleukin-7 (IL-7) and CXCL12 production after Treg depletion suggesting that activated T cells that are generated in the absence of Treg cells may target lineage-specific BM niche cells, resulting in defective lymphopoiesis from HSC. Our results suggest that Treg cells regulate the production of important growth factors for lymphopoiesis and are crucial for maintaining niche activity and for preserving the function of HSC. These results provide new insights into Treg cells biology and function and are relevant for further clinical application for the modulation of immune reconstitution defects after transplantation
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