Opposing roles for RelB and Bcl-3 in regulation of T-box expressed in T cells, GATA-3, and Th effector differentiation.

Corn RA, Hunter C, Liou HC, Siebenlist U, Boothby MR
J Immunol. 2005 175 (4): 2102-10

PMID: 16081776 · DOI:10.4049/jimmunol.175.4.2102

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.

MeSH Terms (21)

Animals B-Cell Lymphoma 3 Protein Cell Differentiation Cells, Cultured DNA-Binding Proteins GATA3 Transcription Factor Humans Interferon-gamma Jurkat Cells Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Polycomb Repressive Complex 1 Proto-Oncogene Proteins Proto-Oncogene Proteins c-rel T-Box Domain Proteins T-Lymphocytes, Helper-Inducer Th1 Cells Th2 Cells Transcription Factors

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