Department of Biomedical Sciences, Hanyang University Graduate School, Seoul, Korea.
Eur J Immunol. 2015 Jan;45(1):167-79. doi: 10.1002/eji.201444532. Epub 2014 Dec 1.
Foxp3(+) Treg cells are crucial for maintaining T-cell homeostasis, but their role in B-cell homeostasis remains unclear. Here, we found that Foxp3 mutant scurfy mice had fewer B-lineage cells and progenitors, including common lymphoid progenitors and lymphoid-primed multipotent progenitors, but higher myeloid-lineage cell numbers in BM compared with WT littermates. Homeostasis within the HSC compartment was also compromised with apparent expansion of long- and short-term HSCs. This abnormality was due to the lack of Treg cells, but not to the Treg-cell extrinsic functions of Foxp3 or cell-autonomous defects. Among cytokines enriched in the BM of scurfy mice, IFN-γ affected only B lymphopoiesis, but GM-CSF, TNF, and IL-6 collectively promoted granulopoiesis at the expense of B lymphopoiesis. Neutralization of these three cytokines reversed the hematopoietic defects on early B-cell progenitors in scurfy mice. Treg cells ensured B lymphopoiesis by reducing the production of these cytokines by effector T cells, but not by directly affecting B lymphopoiesis. These results suggest that Treg cells occupy an important niche in the BM to protect B-lineage progenitor cells from excessive exposure to a lymphopoiesis-regulating milieu.
Foxp3(+)Treg 细胞对于维持 T 细胞的内稳态至关重要，但它们在 B 细胞内稳态中的作用尚不清楚。在这里，我们发现 Foxp3 突变的 scurfy 小鼠骨髓中 B 细胞谱系细胞和祖细胞（包括普通淋巴祖细胞和淋巴样前体多能祖细胞）数量减少，但髓系细胞数量增加，与 WT 同窝仔相比。HSC 池内的内稳态也受到影响，长时和短时 HSC 明显扩张。这种异常是由于缺乏 Treg 细胞引起的，而不是由于 Foxp3 的 Treg 细胞外在功能或细胞自主缺陷引起的。在 scurfy 小鼠骨髓中富集的细胞因子中，IFN-γ仅影响 B 细胞生成，但 GM-CSF、TNF 和 IL-6 共同促进粒细胞生成，而牺牲 B 细胞生成。这三种细胞因子的中和逆转了 scurfy 小鼠早期 B 细胞祖细胞的造血缺陷。Treg 细胞通过减少效应 T 细胞产生这些细胞因子来确保 B 细胞生成，而不是直接影响 B 细胞生成。这些结果表明，Treg 细胞在骨髓中占据重要位置，以保护 B 细胞谱系祖细胞免受过度暴露于调节淋巴细胞生成的环境中。
