Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University, 269W. Campus Drive, Stanford, California 94305, USA.
Department of Medicine, Hematopoietic Stem Cell Transplantation Program, University of Perugia, Piazzale Menghini, 06132, Sant'Andrea delle Fratte, Perugia 06132, Italy.
Nat Commun. 2017 May 9;8:15068. doi: 10.1038/ncomms15068.
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.
叉头框蛋白 3（Foxp3）调节性 T 细胞（Treg 细胞）调节免疫系统并维持自身耐受，但它们是否影响造血或造血干细胞（HSC）介导的移植后重建尚不清楚。在这里，我们表明 Treg 细胞耗竭小鼠的 B 细胞淋巴发生受损，但这种减少的 B 细胞淋巴发生可通过将受影响的 HSCs 或骨髓细胞过继转移到 Treg 细胞功能正常的受体中而得到挽救。使用 Treg 细胞耗竭小鼠作为受体进行同种和异种移植时，B 细胞重建均被阻断。Treg 细胞可以控制生理 IL-7 的产生，IL-7 对于正常的 B 细胞淋巴发生是必不可少的，主要由血管周基质细胞中 ICAM1 的一个亚群维持。我们的研究表明，Treg 细胞通过维持骨髓微环境中的免疫稳态对于 HSCs 中的 B 细胞分化是重要的，无论是在生理条件下还是在骨髓移植后。
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