Clusterin synergizes with IL-2 for the expansion and IFN-γ production of natural killer cells

Journal of Leukocyte Biology

Jeffrey A Bluestone²  Young-Joo Hong¹  Young-Bin Yu¹  Young-Jun Shim³  Chung Hee Sonn¹  Bon-Hong Min , and³  Kyung-Mi Lee¹ 

[1] Departments of Biochemistry and Molecular Biology and  Pharmacology, Division of Brain KoreaProgram for Biomedical Science, Korea University College of Medicine, Seoul, Korea;Diabetes Center, and Department of Medicine, University of California, San Francisco, San Francisco, California, USA  Pharmacology, Division of Brain KoreaProgram for Biomedical Science, Korea University College of Medicine, Seoul, Korea; Pharmacology, Division of Brain KoreaProgram for Biomedical Science, Korea University College of Medicine, Seoul, Korea;

关键词: cell proliferation;    NK activation markers;    natural cytotoxicity;    immune function;   

DOI  :  10.1189/jlb.0310157

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CLU is a secreted, multifunctional protein implicated in several immunologic and pathologic conditions. As the level of serum CLU was shown to be elevated during inflammatory responses, we questioned if CLU might interact with circulating lymphocytes leading to functional consequences. To assess this possibility directly, mouse splenocytes and purified NK cells were cultured with varying dose of CLU, and its effect on cell proliferation was examined. Our data showed that CLU up-regulated DNA synthesis and expansion of NK cells significantly in response to a suboptimal, but not maximal, dose of IL-2, and CLU alone did not exhibit such effects. This CLU-mediated synergy required the copresence of CLU at the onset of IL-2 stimulation and needed a continuous presence during the rest of the culture. Importantly, NK cells stimulated with CLU showed increased formation of cell clusters and a CD69 activation receptor, representing a higher cellular activation status compared with those from the control group. Furthermore, these NK cells displayed elevated IFN-γ production upon RMA/S tumor target exposures, implying that CLU regulates not only NK cell expansion but also effector function of NK cells. Collectively, our data present a previously unrecognized function of CLU as a novel regulator of NK cells via providing costimulation required for cell proliferation and IFN-γ secretion. Therefore, the role of CLU on NK cells should be taken into consideration for the previously observed, diverse functions of CLU in chronic inflammatory and autoimmune conditions.

【 授权许可】

Unknown