Foxp3(+) regulatory T cells ensure B lymphopoiesis by inhibiting the granulopoietic activity of effector T cells in mouse bone marrow
- Authors
- Kim, Sunghoon; Park, Kyungsoo; Choi, Jinwook; Jang, Eunkyeong; Paik, Doo-Jin; Seong, Rho H.; Youn, Jeehee
- Issue Date
- Jan-2015
- Publisher
- WILEY-BLACKWELL
- Keywords
- B lymphopoiesis; Foxp3; Granulopoietins; Hematopoiesis; Regulatory T cells
- Citation
- EUROPEAN JOURNAL OF IMMUNOLOGY, v.45, no.1, pp.167 - 179
- Indexed
- SCIE
SCOPUS
- Journal Title
- EUROPEAN JOURNAL OF IMMUNOLOGY
- Volume
- 45
- Number
- 1
- Start Page
- 167
- End Page
- 179
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/158119
- DOI
- 10.1002/eji.201444532
- ISSN
- 0014-2980
- 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.
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