| T-cell and B-cell signaling biomarkers and treatment targets in lupus. | |
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MedLine Citation:
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PMID: 19550330 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE OF REVIEW: Systemic lupus erythematosus is characterized by the production of antinuclear autoantibodies and dysfunction of T-cells, B-cells, and dendritic cells. Here, we review newly recognized genetic factors and mechanisms that underlie abnormal intracellular signal processing and intercellular communication within the immune system in systemic lupus erythematosus. RECENT FINDINGS: Activation of the mammalian target of rapamycin plays a pivotal role in abnormal activation of T and B-cells in systemic lupus erythematosus. In T-cells, increased production of nitric oxide and mitochondrial hyperpolarization were identified as metabolic checkpoints upstream of mammalian target of rapamycin activation. Mammalian target of rapamycin controls the expression T-cell receptor-associated signaling proteins CD4 and CD3zeta through increased expression of the endosome recycling regulator HRES-1/Rab4 gene, mediates enhanced Ca2+ fluxing and skews the expression of tyrosine kinases both in T and B-cells, and blocks the expression of Foxp3 and the expansion of regulatory T-cells. Mitochondrial hyperpolarization and the resultant ATP depletion predispose T-cells to necrosis, thus promoting the dendritic cell activation, antinuclear autoantibody production, and inflammation. SUMMARY: Mitochondrial hyperpolarization, increased activity of mammalian target of rapamycin and Syk kinases, enhanced receptor recycling and Ca2+ flux have emerged as common T and B-cell biomarkers and targets for treatment in systemic lupus erythematosus. |
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Authors:
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Andras Perl; David R Fernandez; Tiffany Telarico; Edward Doherty; Lisa Francis; Paul E Phillips |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Current opinion in rheumatology Volume: 21 ISSN: 1531-6963 ISO Abbreviation: Curr Opin Rheumatol Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-13 Completed Date: 2009-11-04 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9000851 Medline TA: Curr Opin Rheumatol Country: United States |
Other Details:
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Languages: eng Pagination: 454-64 Citation Subset: IM |
Affiliation:
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Division of Rheumatology, Department of Medicine, State University of New York, Upstate Medical University, College of Medicine, Syracuse, New York 13210, USA. perla@upstate.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals B-Lymphocytes / immunology*, metabolism Biological Markers / metabolism Calcium Signaling Endocytosis Humans Lupus Erythematosus, Systemic / immunology*, metabolism, therapy Mitochondria / metabolism Models, Biological Oxidative Stress Protein Kinases / metabolism Receptors, Antigen, B-Cell / metabolism Signal Transduction T-Lymphocytes / immunology*, metabolism rab4 GTP-Binding Proteins / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI 048079/AI/NIAID NIH HHS; AI 061066/AI/NIAID NIH HHS; AI 072648/AI/NIAID NIH HHS; AR056957/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Receptors, Antigen, B-Cell; EC 2.7.-/Protein Kinases; EC 2.7.1.-/mTOR protein; EC 3.6.5.2/rab4 GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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