title: Spleen tyrosine kinase (Syk) regulates systemic lupus erythematosus (SLE) T cell signaling.
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.
authors.affiliation: Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Alexandros P
authors.initials: AP
authors.lastname: Grammatikos
authors.forename: Debjani
authors.initials: D
authors.lastname: Ghosh
authors.forename: Amy
authors.initials: A
authors.lastname: Devlin
authors.forename: Vasileios C
authors.initials: VC
authors.lastname: Kyttaris
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D000328:Adult; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054648:Protein Phosphatase 2 / Q000096:biosynthesis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000201:enzymology* / Q000473:pathology; D000098546:Interleukin-21
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D054648:Protein Phosphatase 2; D000098546:Interleukin-21