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

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

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-betdeficient HPC, suggesting that T-bet is required for OPNmediated NK development. Collectively, these results show that paracrine OPN signaling drives NK-lineage commitment, thus ultimately promoting NK cell development.

HEMATOPOIETIC stem cells; KILLER cells; INTERLEUKINS; GROWTH factors; OSTEOPONTIN; CELL adhesion molecules

Stem Cells, 2008, Vol 26, Issue 8, p2114

1066-5099

Academic Journal

10.1634/stemcells.2008-0370