| Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. | |
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MedLine Citation:
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PMID: 21389264 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a breakdown of tolerance to nuclear antigens and the development of immune complexes. Genomic approaches have shown that human SLE leukocytes homogeneously express type I interferon (IFN)-induced and neutrophil-related transcripts. Increased production and/or bioavailability of IFN-α and associated alterations in dendritic cell (DC) homeostasis have been linked to lupus pathogenesis. Although neutrophils have long been shown to be associated with lupus, their potential role in disease pathogenesis remains elusive. Here, we show that mature SLE neutrophils are primed in vivo by type I IFN and die upon exposure to SLE-derived anti-ribonucleoprotein antibodies, releasing neutrophil extracellular traps (NETs). SLE NETs contain DNA as well as large amounts of LL37 and HMGB1, neutrophil proteins that facilitate the uptake and recognition of mammalian DNA by plasmacytoid DCs (pDCs). Indeed, SLE NETs activate pDCs to produce high levels of IFN-α in a DNA- and TLR9 (Toll-like receptor 9)-dependent manner. Our results reveal an unsuspected role for neutrophils in SLE pathogenesis and identify a novel link between nucleic acid-recognizing antibodies and type I IFN production in this disease. |
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Authors:
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Gina S Garcia-Romo; Simone Caielli; Barbara Vega; John Connolly; Florence Allantaz; Zhaohui Xu; Marilynn Punaro; Jeanine Baisch; Cristiana Guiducci; Robert L Coffman; Franck J Barrat; Jacques Banchereau; Virginia Pascual |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; 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: 2012-03-12 |
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: 73ra20 Citation Subset: IM |
Affiliation:
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Baylor Institute for Immunology Research, Dallas, TX 752014, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE27427 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Antibodies, Antinuclear / blood Apoptosis / immunology Autoantibodies / blood Case-Control Studies Child Dendritic Cells / immunology Gene Expression Profiling Humans Interferon Type I / biosynthesis* Lupus Erythematosus, Systemic / blood, genetics, immunology* NADP / blood Neutrophils / immunology*, pathology Oligonucleotide Array Sequence Analysis Receptors, IgG / blood Ribonucleoproteins / immunology Toll-Like Receptor 7 / blood |
| Grant Support | |
ID/Acronym/Agency:
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AR054083-01/AR/NIAMS NIH HHS; ARO55503-01//PHS HHS; P50 AR054083-01/AR/NIAMS NIH HHS; P50 AR054083-02/AR/NIAMS NIH HHS; P50 AR054083-03/AR/NIAMS NIH HHS; P50 AR054083-04/AR/NIAMS NIH HHS; P50 AR054083-04S1/AR/NIAMS NIH HHS; P50 AR054083-05/AR/NIAMS NIH HHS; R01 AR050770-01/AR/NIAMS NIH HHS; R01 AR050770-01/AR/NIAMS NIH HHS; R01 AR050770-02/AR/NIAMS NIH HHS; R01 AR050770-03/AR/NIAMS NIH HHS; R01 AR050770-04/AR/NIAMS NIH HHS; R01 AR050770-05A1/AR/NIAMS NIH HHS; R01 AR050770-06/AR/NIAMS NIH HHS; R01 AR050770-07/AR/NIAMS NIH HHS; R01 AR050770-08/AR/NIAMS NIH HHS; R01 CA078846-01A1/CA/NCI NIH HHS; R01 CA078846-02/CA/NCI NIH HHS; R01 CA078846-03/CA/NCI NIH HHS; R01 CA078846-04/CA/NCI NIH HHS; R01 CA078846-05/CA/NCI NIH HHS; R01 CA078846-06/CA/NCI NIH HHS; R01 CA078846-07/CA/NCI NIH HHS; R01 CA078846-08/CA/NCI NIH HHS; R01 CA078846-09/CA/NCI NIH HHS; R01 CA078846-10/CA/NCI NIH HHS; R01-CA078846/CA/NCI NIH HHS; U19 AI057234-01/AI/NIAID NIH HHS; U19 AI057234-02/AI/NIAID NIH HHS; U19 AI057234-03/AI/NIAID NIH HHS; U19 AI057234-04/AI/NIAID NIH HHS; U19 AI057234-05/AI/NIAID NIH HHS; U19 AI057234-05S1/AI/NIAID NIH HHS; U19 AI057234-06/AI/NIAID NIH HHS; U19 AI057234-06S1/AI/NIAID NIH HHS; U19 AI057234-06S2/AI/NIAID NIH HHS; U19 AI057234-06S3/AI/NIAID NIH HHS; U19 AI057234-07/AI/NIAID NIH HHS; U19 AI057234-07S1/AI/NIAID NIH HHS; U19 AI057234-08/AI/NIAID NIH HHS; U19 AI057234-09/AI/NIAID NIH HHS; U19 AI082715-01/AI/NIAID NIH HHS; U19 AI082715-02/AI/NIAID NIH HHS; U19 AI082715-03/AI/NIAID NIH HHS; U19 AI082715-04/AI/NIAID NIH HHS; U19-A1057234//PHS HHS; U19-AI082715-01/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Antinuclear; 0/Autoantibodies; 0/Fc gamma receptor IIA; 0/Interferon Type I; 0/Receptors, IgG; 0/Ribonucleoproteins; 0/TLR7 protein, human; 0/Toll-Like Receptor 7; 53-59-8/NADP |
| Comments/Corrections | |
Comment In:
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EMBO Mol Med. 2011 Oct;3(10):578-80
[PMID:
21905225
]
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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