1. The NF-κB regulator Bcl-3 governs dendritic cell antigen presentation functions in adaptive immunity.
- Author
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Tassi I, Claudio E, Wang H, Tang W, Ha HL, Saret S, Ramaswamy M, Siegel R, and Siebenlist U
- Subjects
- Animals, B-Cell Lymphoma 3 Protein, CD11c Antigen metabolism, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Cell Differentiation, Cell Survival genetics, Dendritic Cells cytology, Dendritic Cells metabolism, Gene Expression, Lymphocyte Activation immunology, Mice, Mice, Knockout, Proto-Oncogene Proteins genetics, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Transcription Factors genetics, Antigen Presentation, Dendritic Cells immunology, NF-kappa B metabolism, Proto-Oncogene Proteins metabolism, Transcription Factors metabolism
- Abstract
Bcl-3 is an atypical member of the IκB family and modulates gene expression via interaction with p50/NF-κB1 or p52/NF-κB2 homodimers. We report in the present study that Bcl-3 is required in dendritic cells (DCs) to assure effective priming of CD4 and CD8 T cells. Lack of Bcl-3 in bone marrow-derived DCs blunted their ability to expand and promote effector functions of T cells upon Ag/adjuvant challenge in vitro and after adoptive transfers in vivo. Importantly, the critical role of Bcl-3 for priming of T cells was exposed upon Ag/adjuvant challenge of mice specifically ablated of Bcl-3 in DCs. Furthermore, Bcl-3 in endogenous DCs was necessary for contact hypersensitivity responses. Bcl-3 modestly aided maturation of DCs, but most consequentially, Bcl-3 promoted their survival, partially inhibiting expression of several antiapoptotic genes. Loss of Bcl-3 accelerated apoptosis of bone marrow-derived DCs during Ag presentation to T cells, and DC survival was markedly impaired in the context of inflammatory conditions in mice specifically lacking Bcl-3 in these cells. Conversely, selective overexpression of Bcl-3 in DCs extended their lifespan in vitro and in vivo, correlating with increased capacity to prime T cells. These results expose a previously unidentified function for Bcl-3 in DC survival and the generation of adaptive immunity.
- Published
- 2014
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