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- Title
Spleen Tyrosine Kinase (Syk) Regulates Systemic Lupus Erythematosus (SLE) T Cell Signaling.
- Authors
Grammatikos, Alexandros P.; Ghosh, Debjani; Devlin, Amy; Kyttaris, Vasileios C.; Tsokos, George C.
- Abstract
Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk is being considered as a therapeutic target we asked whether Syk is central to the multiple aberrantly modulated molecules in SLE T cells. Using a gene expression array, we demonstrate that forced expression of Syk in normal T cells reproduces most of the aberrantly expressed molecules whereas silencing of Syk in SLE T cells normalizes the expression of most abnormally expressed molecules. Protein along with gene expression modulation for select molecules was confirmed. Specifically, levels of cytokine IL-21, cell surface receptor CD44, and intracellular molecules PP2A and OAS2 increased following Syk overexpression in normal T cells and decreased after Syk silencing in SLE T cells. Our results demonstrate that levels of Syk affect the expression of a number of enzymes, cytokines and receptors that play a key role in the development of disease pathogenesis in SLE and provide support for therapeutic targeting in SLE patients.
- Subjects
PROTEIN-tyrosine kinases; SPLEEN; SYSTEMIC lupus erythematosus; CELLULAR signal transduction; GENETIC regulation; T cell receptors; GENE expression; BIOLOGICAL assay
- Publication
PLoS ONE, 2013, Vol 8, Issue 8, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0074550