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Osteopontin promotes the development of natural killer cells from hematopoietic stem cells

Authors
Chung, Jin WoongKim, Mi SunPiao, Zheng-HaoJeong, MiraYoon, Suk RanShin, NaraKim, Sang YongHwang, Eun SookYang, YoungLee, Young HoKim, Young SangChoi, Inpyo
Issue Date
Jan-2009
Publisher
WILEY-BLACKWELL
Keywords
hematopoietic stem cells; natural killer cells; interleukin-15; osteopontin
Citation
STEM CELLS, v.26, no.8, pp 2114 - 2123
Pages
10
Journal Title
STEM CELLS
Volume
26
Number
8
Start Page
2114
End Page
2123
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/14215
DOI
10.1634/stemcells.2008-0370
ISSN
1066-5099
1549-4918
Abstract
The detailed mechanisms driving the development of natural killer (NK) cells from hematopoietic stem cells remain to be clearly elucidated. Here, we show that osteopontin (OPN) is a key factor for NK development. OPN-deficient mice evidenced severe impairments of NK development in bone marrow (BM) and spleen in which the NK populations that express CD122 and NK cell receptors were reduced. However, the absence of intrinsic OPN expression did not affect NK development, whereas the absence of OPN in the microenvironment caused a significant reduction in NK population. The expression of OPN was induced by interieukin (IL)-15 in BM stromal cells, and the defect in NK differentiation in IL-15(-/-) hematopoietic precursor cells (HPC) was recovered by addition of recombinant OPN, suggesting that the microenvironmental OPN may be a key factor in IL-15-mediated NK differentiation. In addition, OPN-driven NK maturation was reduced in T-bet-deficient HPC, suggesting that T-bet is required for OPN-mediated NK development. Collectively, these results show that paracrine OPN signaling drives NK-lineage commitment, thus ultimately promoting NK cell development.
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