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International Immunology Advance Access originally published online on November 13, 2007
International Immunology 2008 20(1):71-79; doi:10.1093/intimm/dxm120
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Runx proteins are involved in regulation of CD122, Ly49 family and IFN-{gamma} expression during NK cell differentiation

Shin-ichiro Ohno1, Takehito Sato1, Kazuyoshi Kohu2, Kazuyoshi Takeda3, Ko Okumura3, Masanobu Satake2 and Sonoko Habu1

1 Department of Immunology, Tokai University School of Medicine, Boseidai, Isehara, Kanagawa 259-1193, Japan
2 Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi, Aobaku, Sendai, Japan
3 Department of Immunology, Juntendo University School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan

Correspondence to: T. Sato; E-mail: takehito{at}is.icc.u-tokai.ac.jp

Runx family proteins play indispensable roles in the development of various hematopoietic lineage cells. However, their function in NK cells is still uncertain. We found that NK cells and CD8 T cells dominantly express Runx3 protein, whereas NKT cells and CD4 T cells express Runx1. Reverse transcription–PCR analysis revealed that Runx3 expression is initiated at the NK precursor stage and is maintained along the course of NK cell differentiation. In order to examine their role in the earlier stage of NK cell development, we introduced Runx dominant-negative (Runx dn) form into Lin–c-kit+Sca-1+ hematopoietic stem cells, which were applied to NK cell-inducing culture. Post-cultured cells showed a decreased expression of IL-2/IL-15 common receptor beta subunit (CD122), consistent with another finding that Runx binds to promoter region of CD122 gene. To examine the Runx function in the later developmental stage, we used transgenic mouse, in which Runx dn form is expressed in immature and mature NK cells. This mouse showed decreased expressions of NK maturation markers, such as Ly49 family, Mac-1 and CD43, whereas IFN-{gamma} production was greatly enhanced. These findings suggest that Runx proteins, especially Runx3, play multiple roles in NK cell differentiation.

Keywords: differentiation, NK cell, Runx

Transmitting editor: T. Watanabe

Received 21 February 2007, accepted 17 October 2007.


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