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

Woong Chung Jin, Sun Kim Mi, Zheng Hao Piao, Mira Jeong, Ran Yoon Suk, Nara Shin, Yong Kim Sang, Sook Hwang Eun, Young Yang, Ho Lee Young, Sang Kim Young, Inpyo Choi

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish
Pages (from-to)2114-2123
Number of pages10
JournalStem Cells
Volume26
Issue number8
DOIs
StatePublished - Aug 2008

Keywords

  • Hematopoietic stem cells
  • Interleukin-15
  • Natural killer cells
  • Osteopontin

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