Document Detail


Functional genetic polymorphisms in ILT3 are associated with decreased surface expression on dendritic cells and increased serum cytokines in lupus patients.
MedLine Citation:
PMID:  22904259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Hyperactivity of the type I interferon (IFN) pathway is involved in the pathogenesis of systemic lupus erythematosus (SLE). Immunoglobulin like transcript (ILT3) is an immunohibitory transmembrane molecule which is induced by type I IFNs. ILT3 is expressed by plasmacytoid dendritic cells (PDCs), monocytoid dendritic cells (MDCs), and monocytes/macrophages. Given the pathogenic role of IFN in SLE, we hypothesised that the IFN-induced immunosuppressive ILT3 receptor may be dysfunctional in human SLE.
METHODS: 132 European-derived and 79 Hispanic-American SLE patients were genotyped for two coding-change single nucleotide polymorphisms (SNPs) predicted to interfere with protein folding in ILT3 (rs11540761 and rs1048801). 116 control DNA samples and sera from healthy controls were also studied. We detected associations between ILT3 genotype and serum cytokine profiles. ILT3 expression levels on PDCs and MDCs from 18 patients and 10 controls were studied by flow cytometry.
RESULTS: The rs11540761 SNP in the extracellular region was associated with decreased cell surface expression of ILT3 on circulating MDCs and to a lesser extent PDCs in SLE patients. The cytoplasmically located rs1048801 SNP was not associated with a change in dendritic cells expression of ILT3. Both SNPs were significantly and independently associated with increased levels of serum type I IFN activity in SLE patients. The rs1048801 SNP was also associated with increased serum levels of TNF-α.
CONCLUSIONS: Loss-of-function polymorphisms in ILT3 are associated with increased inflammatory cytokine levels in SLE, supporting a biological role for ILT3 in SLE.
Authors:
Mark A Jensen; Karen C Patterson; Akaash A Kumar; Marissa Kumabe; Beverly S Franek; Timothy B Niewold
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-17
Journal Detail:
Title:  Annals of the rheumatic diseases     Volume:  72     ISSN:  1468-2060     ISO Abbreviation:  Ann. Rheum. Dis.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-04-30     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  0372355     Medline TA:  Ann Rheum Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  596-601     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antigens, Surface / genetics,  immunology
Cells, Cultured
Cytokines / blood,  immunology
Dendritic Cells / cytology,  immunology*,  metabolism
Genotype
Humans
Interferon-gamma / secretion
Lupus Erythematosus, Systemic / genetics*,  immunology*,  metabolism
Macrophages / cytology,  immunology,  metabolism
Monocytes / cytology,  immunology,  metabolism
Polymorphism, Single Nucleotide / genetics,  immunology
Receptors, Cell Surface / blood*,  genetics*,  immunology
Grant Support
ID/Acronym/Agency:
AI071651/AI/NIAID NIH HHS; K08 AI083790/AI/NIAID NIH HHS; K08 AI083790/AI/NIAID NIH HHS; L30 AI071651/AI/NIAID NIH HHS; P30 DK42086/DK/NIDDK NIH HHS; R01 AR060861/AR/NIAMS NIH HHS; R01 AR060861/AR/NIAMS NIH HHS; UL1 RR024999/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Surface; 0/Cytokines; 0/LILRB4 protein, human; 0/Receptors, Cell Surface; 82115-62-6/Interferon-gamma
Comments/Corrections

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