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PMID: 20001421 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Systems biology of lupus: mapping the impact of genomic and environmental factors on gene expression signatures, cellular signaling, metabolic pathways, hormonal and cytokine imbalance, and selecting targets for treatment.

Autoimmunity ·Vol. 43 ·No. 1 ·2010-02-00 ·Pages 32-47

Perl A

Abstract

Systemic lupus erythematosus (SLE) is characterized by the dysfunction of T cells, B cells, and dendritic cells, the release of pro-inflammatory nuclear materials from necrotic cells, and the formation of antinuclear antibodies (ANA) and immune complexes of ANA with DNA, RNA, and nuclear proteins. Activation of the mammalian target of rapamycin (mTOR) has recently emerged as a key factor in abnormal activation of T and B cells in SLE. In T cells, increased production of nitric oxide and mitochondrial hyperpolarization (MHP) were identified as metabolic checkpoints upstream of mTOR activation. mTOR controls the expression T-cell receptor-associated signaling proteins CD4 and CD3zeta through increased expression of the endosome recycling regulator Rab5 and HRES-1/Rab4 genes, enhances Ca2+ fluxing and skews the expression of tyrosine kinases both in T and B cells, and blocks the expression of Foxp3 and the generation of regulatory T cells. MHP, increased activity of mTOR, Rab GTPases, and Syk kinases, and enhanced Ca2+ flux have emerged as common T and B cell biomarkers and targets for treatment in SLE.

MeSH Terms
B-Lymphocytes/immunology Cytokines/immunology Gene Expression Humans Lupus Erythematosus, Systemic/genetics,immunology,metabolism Signal Transduction Systems Biology T-Lymphocytes/immunology
Chemicals
Cytokines
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Perl Andras
Division of Rheumatology, Departments of Medicine and Microbiology and Immunology, College of Medicine, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA. perla@upstate.edu
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Article Info
Journal
Autoimmunity
Abbr.
Autoimmunity
ISSN
1607-842X
DOI
10.3109/08916930903374774
Email
perla@upstate.edu
Published
2010-02-00
Pages
32-47
Language
English
Region
England
NLM ID
8900070
PMCID
PMC4020422
Subset
IM
Grants
NIAID NIH HHS · AI 061066 · United States
NIAID NIH HHS · R56 AI048079 · United States
NIAID NIH HHS · AI 048079 · United States
NIAID NIH HHS · AI 072648 · United States
NIAID NIH HHS · R01 AI048079 · United States
NIAID NIH HHS · R21 AI061066 · United States
NIAID NIH HHS · R01 AI072648 · United States
External Links
PubMed source DOI: 10.3109/08916930903374774 PMC Full Text View journal details
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