Gene interactions and pathways from curated databases and text-mining
Curr Opin Rheumatol 2009, PMID: 19550330

T-cell and B-cell signaling biomarkers and treatment targets in lupus.

Perl, Andras; Fernandez, David R; Telarico, Tiffany; Doherty, Edward; Francis, Lisa; Phillips, Paul E

OBJECTIVE

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.

RESULTS

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.

CONCLUSIONS

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.

Diseases/Pathways annotated by Medline MESH: Calcium Signaling, Lupus Erythematosus, Systemic
Document information provided by NCBI PubMed

Text Mining Data

Foxp3 ⊣ Mammalian target of rapamycin: " 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 "

Manually curated Databases

No curated data.