T-cell and B-cell signaling biomarkers and treatment targets in lupus
| Autor: | David Fernandez, Edward Doherty, Tiffany Telarico, Lisa Francis, Paul E. Phillips, Andras Perl |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Receptor recycling
T cell T-Lymphocytes Receptors Antigen B-Cell Models Biological Article Rheumatology immune system diseases medicine Animals Humans Lupus Erythematosus Systemic Calcium Signaling skin and connective tissue diseases B cell B-Lymphocytes Systemic lupus erythematosus Lupus erythematosus business.industry rab4 GTP-Binding Proteins TOR Serine-Threonine Kinases Autoantibody medicine.disease Endocytosis Mitochondria Oxidative Stress medicine.anatomical_structure Immunology Signal transduction business Protein Kinases Intracellular Biomarkers Signal Transduction |
| Popis: | 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.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.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. |
| Databáze: | OpenAIRE |
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