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This Article Free via Open Access: OA OA Full Text Full Text (PDF) Supplemental Data OA All Versions of this Article: 2008-0370v1 26/8/2114    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chung, J. W. Articles by Choi, I. Search for Related Content PubMed PubMed Citation Articles by Chung, J. W. Articles by Choi, I.

TISSUE-SPECIFIC STEM CELLS

Osteopontin Promotes the Development of Natural Killer Cells from Hematopoietic Stem Cells

^aStem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon, Republic of Korea;
^bDivision of Molecular Life Sciences and College of Pharmacy, Ewha Women's University, Seoul, Republic of Korea;
^cDepartment of Life Science, Sookmyung Women's University, Yongsan-Gu, Seoul, Republic of Korea;
^dDepartment of Pathology, College of Medicine, and
^eDepartment of Biochemistry, College of Natural Sciences, Chungnam National University, Taejon, Republic of Korea

Key Words. Hematopoietic stem cells • Natural killer cells • Interleukin-15 • Osteopontin

Correspondence: Correspondence: Inpyo Choi, Ph.D., Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon 305-333, Republic of Korea. Telephone: 82-42-860-4223; Fax: 82-42-860-4593; e-mail: ipchoi{at}kribb.re.kr

Received on April 14, 2008; accepted for publication on May 21, 2008.

First published online in STEM CELLS EXPRESS  June 5, 2008.

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.