Opposing roles for RelB and Bcl-3 in regulation of T-box expressed in T cells, GATA-3, and Th effector differentiation.
CD4+ T cells with a block in the NF-kappaB signaling pathway exhibit decreases in Th1 responses and diminished nuclear levels of multiple transactivating NF-kappaB/Rel/IkappaB proteins. To determine the lineage-intrinsic contributions of these transactivators to Th differentiation, T cells from mice deficient in specific subunits were cultured in exogenous cytokines promoting either Th1 or Th2 differentiation. RelB-deficient cells exhibited dramatic defects in Th1 differentiation and IFN-gamma production, whereas no consistent defect in either Th1 or Th2 responses was observed with c-Rel-deficient cells. In sharp contrast, Bcl-3-null T cells displayed no defect in IFN-gamma production, but their Th2 differentiation and IL-4, IL-5, and IL-13 production were significantly impaired. The absence of RelB led to a dramatic decrease in the expression of T-box expressed in T cells and Stat4. In contrast, Bcl-3-deficient cells exhibited decreased GATA-3, consistent with evidence that Bcl-3 can transactivate a gata3 promoter. These data indicate that Bcl-3 and RelB exert distinct and opposing effects on the expression of subset-determining transcription factors, suggesting that the characteristics of Th cell responses may be regulated by titrating the stoichiometry of transactivating NF-kappaB/Rel/IkappaB complexes in the nuclei of developing helper effector cells.
Corn
Radiah A
RA
Department of Microbiology, Meharry Medical College, Nashville, TN 37208, USA.
Hunter
Chris
C
Liou
Hsiou-Chi
HC
Siebenlist
Ulrich
U
Boothby
Mark R
MR
D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020569:Proto-Oncogene Proteins c-rel / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism; D020825:T-Box Domain Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D000098815:T-bet Transcription Factor
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000631345:Bcl3 protein, mouse; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C066476:Pcgf6 protein, mouse; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D007371:Interferon-gamma; D063150:Polycomb Repressive Complex 1