title: The NF-κB regulator Bcl-3 governs dendritic cell antigen presentation functions in adaptive immunity.
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.
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Tassi
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Estefania
authors.initials: E
authors.lastname: Claudio
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Hongshan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Wanhu
authors.initials: W
authors.lastname: Tang
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Hye-lin
authors.initials: HL
authors.lastname: Ha
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Sun
authors.initials: S
authors.lastname: Saret
authors.affiliation: Immunoregulation Section, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Madhu
authors.initials: M
authors.lastname: Ramaswamy
authors.affiliation: Immunoregulation Section, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Richard
authors.initials: R
authors.lastname: Siegel
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and usiebenlist@niaid.nih.gov.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Siebenlist
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000081242:B-Cell Lymphoma 3 Protein; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D039521:CD11c Antigen; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors