Opposing roles of NF-kappaB family members in the regulation of NK cell proliferation and production of IFN-gamma.
It is well established that the nuclear factor-kappaB (NF-kappaB) 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-kappaB in accessory cell and T or B cell function, but less is known about the role of NF-kappaB in NK cells. However, several studies have demonstrated that these transcription factors are required for NK cell production of IFN-gamma and proliferation. The studies presented here examine the role of two NF-kappaB 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-gamma, but remain unaffected in their capacity to proliferate. In contrast, p50-/- NK cells have enhanced proliferative and IFN-gamma 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-gamma and chromatin immunoprecipitation assays demonstrated the association of p50 with the IFN-gamma promoter of resting NK cells. Consistent with the in vitro studies, in vivo studies with NF-kappaB gene-deficient mice infected with Toxoplasma gondii revealed that the absence of p50 leads to enhanced NK cell proliferation and production of IFN-gamma. Together, these studies define distinct roles for c-Rel and p50 in the function of NK cells.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6008, USA.
Cristina M
CM
Tato
Nicola
N
Mason
David
D
Artis
Sagi
S
Shapira
Jorge C
JC
Caamano
Jay H
JH
Bream
Hsiou-Chi
HC
Liou
Christopher A
CA
Hunter
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology*; D020569:Proto-Oncogene Proteins c-rel / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology
D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; D011971:Receptors, Immunologic; C098615:p50 natural killer cell receptor; D007371:Interferon-gamma