Opposing roles of NF-jB family members in the regulation of NK cell proliferation and production of IFN-c

It is well established that the nuclear factor-jB (NF-jB) 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-jB in accessory cell and T or B cell function, but less is known about the role of NF-jB in NK cells. However, several studies have demonstrated that these transcription factors are required for NK cell production of IFN-c and proliferation. The studies presented here examine the role of two NF-jB 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-c, but remain unaffected in their capacity to proliferate. In contrast, p50/ NK cells have enhanced proliferative and IFN-c 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-c and chromatin immunoprecipitation assays demonstrated the association of p50 with the IFN-c promoter of resting NK cells. Consistent with the in vitro studies, in vivo studies with NF-jB gene-deficient mice infected with Toxoplasma gondii revealed that the absence of p50 leads to enhanced NK cell proliferation and production of IFN-c. Together, these studies define distinct roles for c-Rel and p50 in the function of NK cells