| Nuclear factor-κB1 controls the functional maturation of dendritic cells and prevents the activation of autoreactive T cells. | |
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MedLine Citation:
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PMID: 22081022 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Mature dendritic cells (DCs) are crucial for the induction of adaptive immune responses and perturbed DC homeostasis can result in autoimmune disease. Either uncontrolled expansion or enhanced survival of DCs can result in a variety of autoimmune diseases in mouse models. In addition, increased maturation signals, through overexpression of surface Toll-like receptors (TLRs) or stimulation by type I interferon (IFN), has been associated with systemic autoimmunity. Whereas recent studies have focused on identifying factors required for initiating the maturation process, the possibility that resting DCs also express molecules that 'hold' them in an immature state has generally not been considered. Here we show that nuclear factor-κB1 (NF-κB1) is crucial for maintaining the resting state of DCs. Self-antigen-pulsed unstimulated DCs that do not express NF-κB1 were able to activate CD8(+) T lymphocytes and induce autoimmunity. We further show that NF-κB1 negatively regulates the spontaneous production of tumor necrosis factor-α (TNF-α), which is associated with increased granzyme B expression in cytotoxic T lymphocytes (CTLs). These findings provide a new perspective on functional DC maturation and a potential mechanism that may account for pathologic T cell activation. |
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Authors:
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Dilan Dissanayake; Håkan Hall; Nancy Berg-Brown; Alisha R Elford; Sara R Hamilton; Kiichi Murakami; Leslie Summers Deluca; Jennifer L Gommerman; Pamela S Ohashi |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-13 |
Journal Detail:
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Title: Nature medicine Volume: - ISSN: 1546-170X ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9502015 Medline TA: Nat Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Ontario, Canada. [2] Department of Immunology, University of Toronto, Toronto, Ontario, Canada. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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