| Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. | |
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MedLine Citation:
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PMID: 21389263 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Systemic lupus erythematosus (SLE) is a severe and incurable autoimmune disease characterized by chronic activation of plasmacytoid dendritic cells (pDCs) and production of autoantibodies against nuclear self-antigens by hyperreactive B cells. Neutrophils are also implicated in disease pathogenesis; however, the mechanisms involved are unknown. Here, we identified in the sera of SLE patients immunogenic complexes composed of neutrophil-derived antimicrobial peptides and self-DNA. These complexes were produced by activated neutrophils in the form of web-like structures known as neutrophil extracellular traps (NETs) and efficiently triggered innate pDC activation via Toll-like receptor 9 (TLR9). SLE patients were found to develop autoantibodies to both the self-DNA and antimicrobial peptides in NETs, indicating that these complexes could also serve as autoantigens to trigger B cell activation. Circulating neutrophils from SLE patients released more NETs than those from healthy donors; this was further stimulated by the antimicrobial autoantibodies, suggesting a mechanism for the chronic release of immunogenic complexes in SLE. Our data establish a link between neutrophils, pDC activation, and autoimmunity in SLE, providing new potential targets for the treatment of this devastating disease. |
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Authors:
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Roberto Lande; Dipyaman Ganguly; Valeria Facchinetti; Loredana Frasca; Curdin Conrad; Josh Gregorio; Stephan Meller; Georgios Chamilos; Rosalie Sebasigari; Valeria Riccieri; Roland Bassett; Hideki Amuro; Shirou Fukuhara; Tomoki Ito; Yong-Jun Liu; Michel Gilliet |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Science translational medicine Volume: 3 ISSN: 1946-6242 ISO Abbreviation: Sci Transl Med Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-10 Completed Date: 2011-07-06 Revised Date: 2011-11-11 |
Medline Journal Info:
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Nlm Unique ID: 101505086 Medline TA: Sci Transl Med Country: United States |
Other Details:
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Languages: eng Pagination: 73ra19 Citation Subset: IM |
Affiliation:
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Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Antinuclear
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blood Antigen-Antibody Complex / blood Autoantigens / blood B-Lymphocytes / immunology Case-Control Studies Cathelicidins / immunology DNA / blood, immunology Dendritic Cells / immunology* Humans Lupus Erythematosus, Systemic / immunology* Lymphocyte Activation Neutrophils / immunology* Peptides / blood, immunology Toll-Like Receptor 9 / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Antinuclear; 0/Antigen-Antibody Complex; 0/Autoantigens; 0/Cathelicidins; 0/Peptides; 0/TLR9 protein, human; 0/Toll-Like Receptor 9; 0/antimicrobial peptide LL-37; 9007-49-2/DNA |
| Comments/Corrections | |
Comment In:
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EMBO Mol Med. 2011 Oct;3(10):578-80
[PMID:
21905225
]
Nat Rev Rheumatol. 2011 May;7(5):252 [PMID: 21468147 ] Sci Transl Med. 2011 Mar 9;3(73):73ps9 [PMID: 21389262 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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