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

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Title
Osteopontin promotes the development of natural killer cells from hematopoietic stem cells
Author(s)
Jin Woong Chung; Mi Sun Kim; Z H Piao; Mi Ra Jeong; Suk Ran Yoon; Nara Shin; S Y Kim; E S Hwang; Y Yang; Y H Lee; Y S Kim; In Pyo Choi
Bibliographic Citation
Stem Cells, vol. 26, no. 8, pp. 2114-2123
Publication Year
2008
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 interleukin (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.
Keyword
Hematopoietic stem cellsInterleukin-15Natural killer cellsOsteopontin
ISSN
1066-5099
Publisher
Wiley
DOI
http://dx.doi.org/10.1634/stemcells.2008-0370
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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