title: The oncoprotein and transcriptional regulator Bcl-3 governs plasticity and pathogenicity of autoimmune T cells.
abstract: Bcl-3 is an atypical member of the IκB family that modulates transcription in the nucleus via association with p50 (NF-κB1) or p52 (NF-κB2) homodimers. Despite evidence attesting to the overall physiologic importance of Bcl-3, little is known about its cell-specific functions or mechanisms. Here we demonstrate a T-cell-intrinsic function of Bcl-3 in autoimmunity. Bcl-3-deficient T cells failed to induce disease in T cell transfer-induced colitis and experimental autoimmune encephalomyelitis. The protection against disease correlated with a decrease in Th1 cells that produced the cytokines IFN-γ and GM-CSF and an increase in Th17 cells. Although differentiation into Th1 cells was not impaired in the absence of Bcl-3, differentiated Th1 cells converted to less-pathogenic Th17-like cells, in part via mechanisms involving expression of the RORγt transcription factor. Thus, Bcl-3 constrained Th1 cell plasticity and promoted pathogenicity by blocking conversion to Th17-like cells, revealing a unique type of regulation that shapes adaptive immunity.
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Wanhu
authors.initials: W
authors.lastname: Tang
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Hongshan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Estefania
authors.initials: E
authors.lastname: Claudio
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Tassi
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Hye-lin
authors.initials: HL
authors.lastname: Ha
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Sun
authors.initials: S
authors.lastname: Saret
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: usiebenlist@niaid.nih.gov.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Siebenlist
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D000081242:B-Cell Lymphoma 3 Protein; D002454:Cell Differentiation / Q000276:immunology; D003092:Colitis / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D018398:Homeodomain Proteins / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000276:immunology; D052003:NF-kappa B p52 Subunit / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000637:transplantation; D058504:Th17 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D018398:Homeodomain Proteins; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C064658:RAG-1 protein; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor