Osteopontin is required for natural killer cell development (138.19)

• Published in: The Journal of immunology (1950) 2009-04, Vol.182 (1_Supplement), p.138-138.19
• Main Authors: Kim, Mi Sun, Piao, Zheng-Hao, Jeong, Mira, Yoon, Suk Ran, Chung, Jin Woong, Choi, Inpyo
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.138.19

Natural killer (NK) cells are bone-marrow-derived lymphocytes, which share a common progenitor with T cells. Although a model of NK development from hematopoietic stem cells (HSC) has previously been proposed, the factors and detailed mechanisms driving the differentiation of NK remain to be clearly elucidated. Here we show that osteopontin(OPN) is an important molecule as microenvironmental factor for NK development. The OPN deficient mice evidenced distinct defects in the NK populations in both BM and spleen. However OPN deficient HSC also effectively induced the development of NK cells as control HSC, while the experiment of coculture system and in vivo transplantation system showed that the development of NK cells significantly was defected when HSC culture with OPN absence stromal cells, and transplanted HSC rarely induced into NK cells in OPN deficient mice. Also, the level of OPN expression is much more in stromal cells than the developing NK cells, confirming that OPN is important factor as microenvironment for NK development. The secretion of OPN was induced stimulation with IL15 in the BM stromal cells. The function of IL15, as major factor in NK development, might occurs through OPN which is one of other ways for NK development. . 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.