title: 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-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.
authors.affiliation: Department of Biomedical Sciences, Hanyang University Graduate School, Seoul, Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Park
authors.forename: Jinwook
authors.initials: J
authors.lastname: Choi
authors.forename: Eunkyeong
authors.initials: E
authors.lastname: Jang
authors.forename: Doo-Jin
authors.initials: DJ
authors.lastname: Paik
authors.forename: Rho H
authors.initials: RH
authors.lastname: Seong
authors.forename: Jeehee
authors.initials: J
authors.lastname: Youn
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000276:immunology; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D061251:Primary Cell Culture; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
chemical_list: D057134:Antibodies, Neutralizing; D051858:Forkhead Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C498833:Foxp3 protein, mouse
keywords: B lymphopoiesis; Foxp3; Granulopoietins; Hematopoiesis; Regulatory T cells