Foxp3(+) regulatory T cells ensure B lymphopoiesis by inhibiting the granulopoietic activity of effector T cells in mouse bone marrow

Abstract

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- 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.