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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2011-7-22
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pubmed:abstractText |
Dendritic cells (DCs) regulate both immunity and tolerance. Here we have shown that the ubiquitin editing enzyme A20 (Tnfaip3) determines the activation threshold of DCs, via control of canonical NF-?B activation. Tnfaip3(fl/fl)Cd11c-cre(+) mice lacking A20 in DCs demonstrated spontaneous proliferation of conventional and double-negative T cells, their conversion to interferon-? (IFN-?)-producing effector cells, and expansion of plasma cells. They developed ds-DNA antibodies, nephritis, the antiphospholipid syndrome, and lymphosplenomegaly-features of systemic lupus erythematosus-and extramedullary hematopoiesis. A20-deficient DCs were resistant to apoptosis, caused by increased sensitivity to CD40L and RANKL prosurvival signals and upregulation of antiapoptotic proteins Bcl-2 and Bcl-x. They captured injected apoptotic cells more efficiently, resisted the inhibitory effects of apoptotic cells, and induced self-reactive effector lymphocytes. Because genetic polymorphisms in TNFAIP3 are associated with human autoimmune disorders, these findings identify A20-mediated control of DC activation as a crucial checkpoint in the development of systemic autoimmunity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1097-4180
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pubmed:author |
pubmed-author:BeyaertRudiR,
pubmed-author:Branco-MadeiraFilipeF,
pubmed-author:De PrijckSofieS,
pubmed-author:ElewautDirkD,
pubmed-author:HammadHamidaH,
pubmed-author:JanssensSophieS,
pubmed-author:KoolMirjamM,
pubmed-author:LambrechtBart NBN,
pubmed-author:MuskensFemkeF,
pubmed-author:ReizisBorisB,
pubmed-author:SzeMozesM,
pubmed-author:WaelputWimW,
pubmed-author:van LooGeertG,
pubmed-author:van PraetJensJ
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
82-96
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pubmed:meshHeading |
pubmed-meshheading:21723156-Animals,
pubmed-meshheading:21723156-Antibodies, Antinuclear,
pubmed-meshheading:21723156-Apoptosis,
pubmed-meshheading:21723156-Autoimmunity,
pubmed-meshheading:21723156-CD40 Ligand,
pubmed-meshheading:21723156-Cell Proliferation,
pubmed-meshheading:21723156-Cells, Cultured,
pubmed-meshheading:21723156-Cysteine Endopeptidases,
pubmed-meshheading:21723156-Dendritic Cells,
pubmed-meshheading:21723156-Humans,
pubmed-meshheading:21723156-Interferon-gamma,
pubmed-meshheading:21723156-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:21723156-Lupus Erythematosus, Systemic,
pubmed-meshheading:21723156-Mice,
pubmed-meshheading:21723156-Mice, Mutant Strains,
pubmed-meshheading:21723156-Mutation,
pubmed-meshheading:21723156-Plasma Cells,
pubmed-meshheading:21723156-RANK Ligand,
pubmed-meshheading:21723156-T-Lymphocytes
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pubmed:year |
2011
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pubmed:articleTitle |
The ubiquitin-editing protein A20 prevents dendritic cell activation, recognition of apoptotic cells, and systemic autoimmunity.
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pubmed:affiliation |
Laboratory of Immunoregulation, Department of Pulmonary Medicine, University Hospital Gent, 9000 Gent, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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