Spleen Tyrosine Kinase (Syk) Regulates Systemic Lupus Erythematosus (SLE) T Cell Signaling

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Amy Devlin (Creator)

Debjani Ghosh (Creator)

Alexandros P. Grammatikos (Creator)

Vasileios C. Kyttaris (Creator)

George C. Tsokos (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

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.

Additional Information

Publication

Other

PLoS ONE; 8:8 p. 1-9

Language: English

Date: 2013

Keywords

Cytokines, Flow cytometry, T cells, Blood donors, Cytokines

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