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Title 

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

Authors 

Jin Woong ChungMi Sun KimZ H PiaoMi Ra JeongSuk Ran YoonNara ShinS Y KimE S HwangY YangY H LeeY S KimIn Pyo Choi

Publisher 

Wiley-Blackwell

Issue Date 

2008

Citation 

Stem Cells, vol. 26, no. 8, pp. 2114-2123

Keywords 

hematopoietic stem cellsinterleukin-15natural killer cellsosteopontinbone marrow cellcell differentiationcell lineagecell maturationcell populationbone Marrow Cells

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.

ISSN 

1066-5099

Link 

http://dx.doi.org/10.1634/stemcells.2008-0370

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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