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PMID:16081776
Citation |
Corn, RA, Hunter, C, Liou, HC, Siebenlist, U and Boothby, MR (2005) Opposing roles for RelB and Bcl-3 in regulation of T-box expressed in T cells, GATA-3, and Th effector differentiation. J. Immunol. 175:2102-10 |
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Abstract |
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. |
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Keywords |
Animals; Cell Differentiation/immunology; Cells, Cultured; DNA-Binding Proteins/physiology; GATA3 Transcription Factor/biosynthesis; GATA3 Transcription Factor/deficiency; GATA3 Transcription Factor/metabolism; Humans; Interferon-gamma/antagonists & inhibitors; Interferon-gamma/biosynthesis; Jurkat Cells; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Proto-Oncogene Proteins/deficiency; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology; Proto-Oncogene Proteins c-rel/biosynthesis; Proto-Oncogene Proteins c-rel/deficiency; Proto-Oncogene Proteins c-rel/metabolism; T-Box Domain Proteins; T-Lymphocytes, Helper-Inducer/cytology; T-Lymphocytes, Helper-Inducer/immunology; Th1 Cells/cytology; Th1 Cells/metabolism; Th2 Cells/metabolism; Transcription Factors/biosynthesis; Transcription Factors/metabolism |
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