Murine Schnurri-2 controls natural killer cell function and lymphoma development

Abstract

Schnurri (Shn)-2 is a large zinc finger-containing protein implicated in cell growth, signal transduction and lymphocyte development. Here, we report that Shn-2-deficient (Shn-2^−/−) mice develop CD3-positive lymphoma spontaneously. In Shn-2^−/− mice, we observed decreased cytotoxicity of natural killer (NK) cells accompanied by decreased expression of perforin and granzyme-B. In addition, phosphorylation of signal transducer and activator of transcription (STAT) 5 was reduced in Shn-2^−/− NK cells, while phosphorylation of STAT3 and protein expression of nuclear factor-κB p65 subunit were enhanced in Shn-2^−/− NK cells. Moreover, cell-surface expression of activation molecules such as CD27, CD69 and CD122 were decreased on Shn-2^−/− NK cells. Thus, Shn-2 is considered to play an important role in the activation and function of NK cells and the development of T cell lymphoma in vivo.

Keywords::

• NK cells
• Schnnuri–2
• spontaneous lymphoma

Acknowledgments

We thank Ms. Kaoru Sugaya, Hikari K. Asou, Miki Kato and Mr. Toshihiro Ito for their excellent technical assistance. This work was supported by Global COE Program (Global Center for Education and Research in Immune System Regulation and Treatment), and City Area Program (Kazusa/Chiba Area) MEXT (Japan), and by grants from the Ministry of Education, Culture, Sports, Science and Technology (Japan) (Grants-in-Aid: for Scientific Research on Priority Areas #17016010; Scientific Research (B) #21390147, Scientific Research (C) #21591808, Young Scientists (B) #22790452, and (JSPS fellows) #2109747, : Special Coordination Funds for Promoting Science and Technology, and : Cancer Translational Research Project), the Ministry of Health, Labor and Welfare (Japan), Uehara Memorial Foundation, Mochida Foundation, and Naito Foundation.

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