Open AccessOsteopontin Promotes the Development of Natural Killer Cells from Hematopoietic Stem Cells
Author(s) -
Chung Jin Woong,
Kim Mi Sun,
Piao ZhengHao,
Jeong Mira,
Yoon Suk Ran,
Shin Nara,
Kim Sang Yong,
Hwang Eun Sook,
Yang Young,
Lee Young Ho,
Kim Young Sang,
Choi Inpyo
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2008-0370
Subject(s) - osteopontin , biology , haematopoiesis , interleukin 12 , microbiology and biotechnology , stromal cell , stem cell , lymphokine activated killer cell , interleukin 21 , natural killer cell , bone marrow , immunology , cancer research , t cell , cytotoxic t cell , immune system , in vitro , biochemistry
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. Disclosure of potential conflicts of interest is found at the end of this article.