TY - JOUR
T1 - Opposing roles of NF-κB family members in the regulation of NK cell proliferation and production of IFN-γ
AU - Tato, Cristina M.
AU - Mason, Nicola
AU - Artis, David
AU - Shapira, Sagi
AU - Caamano, Jorge C.
AU - Bream, Jay H.
AU - Liou, Hsiou Chi
AU - Hunter, Christopher A.
N1 - Funding Information:
We would like to thank the members of the Pathobiology Department for their help and support during the writing of the manuscript. This work is supported by the National Institutes of Health (NIH) Grant AI 46288, Parasitology Training Grant AI07532 and the State of Pennsylvania (C.A.H.); NIH AI50827 (N.M.) and NIH AI061570 (D.A.).
PY - 2006/4
Y1 - 2006/4
N2 - It is well established that the nuclear factor-κB (NF-κB) 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-κB in accessory cell and T or B cell function, but less is known about the role of NF-κB in NK cells. However, several studies have demonstrated that these transcription factors are required for NK cell production of IFN-γ and proliferation. The studies presented here examine the role of two NF-κB 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-γ, but remain unaffected in their capacity to proliferate. In contrast, p50-/- NK cells have enhanced proliferative and IFN-γ 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-γ and chromatin immunoprecipitation assays demonstrated the association of p50 with the IFN-γ promoter of resting NK cells. Consistent with the in vitro studies, in vivo studies with NF-κB gene-deficient mice infected with Toxoplasma gondii revealed that the absence of p50 leads to enhanced NK cell proliferation and production of IFN-γ. Together, these studies define distinct roles for c-Rel and p50 in the function of NK cells.
AB - It is well established that the nuclear factor-κB (NF-κB) 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-κB in accessory cell and T or B cell function, but less is known about the role of NF-κB in NK cells. However, several studies have demonstrated that these transcription factors are required for NK cell production of IFN-γ and proliferation. The studies presented here examine the role of two NF-κB 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-γ, but remain unaffected in their capacity to proliferate. In contrast, p50-/- NK cells have enhanced proliferative and IFN-γ 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-γ and chromatin immunoprecipitation assays demonstrated the association of p50 with the IFN-γ promoter of resting NK cells. Consistent with the in vitro studies, in vivo studies with NF-κB gene-deficient mice infected with Toxoplasma gondii revealed that the absence of p50 leads to enhanced NK cell proliferation and production of IFN-γ. Together, these studies define distinct roles for c-Rel and p50 in the function of NK cells.
KW - Cytokine gene expression regulation
KW - Innate immunity
KW - Natural killer cells
KW - Toxoplasma gondii
KW - Transcription factors
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U2 - 10.1093/intimm/dxh391
DO - 10.1093/intimm/dxh391
M3 - Article
C2 - 16481345
AN - SCOPUS:33645212840
SN - 0953-8178
VL - 18
SP - 505
EP - 513
JO - International Immunology
JF - International Immunology
IS - 4
ER -