International Immunology Advance Access originally published online on February 15, 2006
International Immunology 2006 18(4):505-513; doi:10.1093/intimm/dxh391
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Opposing roles of NF-
B family members in the regulation of NK cell proliferation and production of IFN-
1 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6008, USA
2 Medical Research Council Center for Immune Regulation, School of Medicine, University of Birmingham, Edgbaston, Birmingham, UK
3 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
4 Department of Medicine, Division of Immunology, Cornell University Medical College, New York, NY, USA
Correspondence to: C. A. Hunter; E-mail: chunter{at}phl.vet.upenn.edu
It is well established that the nuclear factor-
B (NF-B) family of transcription factors participates in the regulation of many aspects of innate and adaptive immunity. The majority of these reports have focused on the role of NF-B in accessory cell and T or B cell function, but less is known about the role of NF-B in NK cells. However, several studies have demonstrated that these transcription factors are required for NK cell production of IFN-
and proliferation. The studies presented here examine the role of two NF-B members, c-Rel and p50, in NK cell function. In vitro data revealed that in the absence of c-Rel, NK cells have a defect in their ability to secrete IFN-, but remain unaffected in their capacity to proliferate. In contrast, p50–/– NK cells have enhanced proliferative and IFN- responses compared with wild-type NK cells. The latter findings suggest a role for p50 as a negative regulator of NK cell production of IFN- and chromatin immunoprecipitation assays demonstrated the association of p50 with the IFN- promoter of resting NK cells. Consistent with the in vitro studies, in vivo studies with NF-B gene-deficient mice infected with Toxoplasma gondii revealed that the absence of p50 leads to enhanced NK cell proliferation and production of IFN-. Together, these studies define distinct roles for c-Rel and p50 in the function of NK cells.
Keywords: cytokine gene expression regulation, innate immunity, natural killer cells, Toxoplasma gondii, transcription factors
Transmitting editor: G. Trinchieri
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