PMID- 20001421
OWN - NLM
STAT- MEDLINE
DCOM- 20100318
LR  - 20211020
IS  - 1607-842X (Electronic)
IS  - 0891-6934 (Print)
IS  - 0891-6934 (Linking)
VI  - 43
IP  - 1
DP  - 2010 Feb
TI  - 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.
PG  - 32-47
LID - 10.3109/08916930903374774 [doi]
AB  - 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.
FAU - Perl, Andras
AU  - Perl A
AD  - 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
LA  - eng
GR  - AI 061066/AI/NIAID NIH HHS/United States
GR  - R56 AI048079/AI/NIAID NIH HHS/United States
GR  - AI 048079/AI/NIAID NIH HHS/United States
GR  - AI 072648/AI/NIAID NIH HHS/United States
GR  - R01 AI048079/AI/NIAID NIH HHS/United States
GR  - R21 AI061066/AI/NIAID NIH HHS/United States
GR  - R01 AI072648/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Autoimmunity
JT  - Autoimmunity
JID - 8900070
RN  - 0 (Cytokines)
SB  - IM
MH  - B-Lymphocytes/*immunology
MH  - Cytokines/*immunology
MH  - Gene Expression
MH  - Humans
MH  - Lupus Erythematosus, Systemic/genetics/*immunology/metabolism
MH  - Signal Transduction
MH  - Systems Biology
MH  - T-Lymphocytes/*immunology
PMC - PMC4020422
MID - NIHMS580206
EDAT- 2009/12/17 06:00
MHDA- 2010/03/20 06:00
PMCR- 2014/05/14
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/03/20 06:00 [medline]
PHST- 2014/05/14 00:00 [pmc-release]
AID - 10.3109/08916930903374774 [doi]
PST - ppublish
SO  - Autoimmunity. 2010 Feb;43(1):32-47. doi: 10.3109/08916930903374774.