期刊
BLOOD
卷 120, 期 22, 页码 4352-4362出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-06-438531
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资金
- National Institutes of Health [DK091780, AR54625, AR49659]
- Biomedical Laboratory Research & Development Service of the Veterans Administration Office of Research and Development [5I01BX000105]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR059364, AR056090, AR053607]
- National Institute on Aging [AG040013]
- Georgia Research Alliance
Intermittent parathyroid hormone (iPTH) treatment expands hemopoietic stem and progenitor cells (HSPCs), but the involved mechanisms and the affected HSPC populations are mostly unknown. Here we show that T cells are required for iPTH to expand short-term HSPCs (ST-HSPCs) and improve blood cell engraftment and host survival after BM transplantation. Silencing of PTH/PTH-related protein receptor (PPR) in T cells abrogates the effects of iPTH, thus demonstrating a requirement for direct PPR signaling in T cells. Mechanistically, iPTH expands ST-HSPCs by activating Wnt signaling in HSPCs and stromal cells (SCs) through T-cell production of the Wnt ligand Wnt10b. Attesting to the relevance of Wnt10b, iPTH fails to expand ST-HSPCs in mice with Wnt10b(-/-) T cells. Moreover, iPTH fails to promote engraftment and survival after BM transplantation in Wnt10b null mice. In summary, direct PPR signaling in T cells and the resulting production of Wnt10b play a pivotal role in the mechanism by which iPTH expands ST-HSPCs. The data suggest that T cells may provide pharmacologic targets for HSPC expansion. (Blood. 2012;120(22):4352-4362)
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