Foxp3+ regulatory T cells maintain the bone marrow microenvironment for B cell lymphopoiesis

Foxp3+ 调节性 T 细胞维持骨髓微环境以促进 B 细胞淋巴细胞生成

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作者:Antonio Pierini, Hidekazu Nishikii, Jeanette Baker, Takaharu Kimura, Hye-Sook Kwon, Yuqiong Pan, Yan Chen, Maite Alvarez, William Strober, Andrea Velardi, Judith A Shizuru, Joy Y Wu, Shigeru Chiba, Robert S Negrin

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.

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