Differential expression and molecular associations of Syk in systemic lupus erythematosus T cells

Sandeep Krishnan, Yuang Taung Juang, Bhabadeb Chowdhury, Abigail Magilavy, Carolyn U. Fisher, Hang Nguyen, Madhusoodana P. Nambiar, Vasileios Kyttaris, Arthur Weinstein, Rena Bahjat, Polly Pine, Violeta Rus, George C. Tsokos

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Diminished expression of TCR ζ and reciprocal up-regulation and association of FcRγ with the TCR/CD3 complex is a hallmark of systemic lupus erythematosus (SLE) T cells. In this study we explored whether differential molecular associations of the spleen tyrosine kinase Syk that preferentially binds to FcRγ contribute to pathological amplification of signals downstream of this "rewired TCR" in SLE. We detected higher amounts of Syk expression and activity in SLE compared with normal T cells. Selective inhibition of the activity of Syk reduced the strength of TCR-induced calcium responses and slowed the rapid kinetics of actin polymerization exclusively in SLE T cells. Syk and ZAP-70 also associated differently with key molecules involved in cytoskeletal and calcium signaling in SLE T cells. Thus, while Vav-1 and LAT preferentially bound to Syk, phospholipase C-γ1 bound to both Syk and ZAP-70. Our results show that differential associations of Syk family kinases contribute to the enhanced TCR-induced signaling responses in SLE T cells. Thus, we propose molecular targeting of Syk as a measure to control abnormal T cell responses in SLE.

Original languageEnglish (US)
Pages (from-to)8145-8152
Number of pages8
JournalJournal of Immunology
Volume181
Issue number11
DOIs
StatePublished - Dec 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Krishnan, S., Juang, Y. T., Chowdhury, B., Magilavy, A., Fisher, C. U., Nguyen, H., Nambiar, M. P., Kyttaris, V., Weinstein, A., Bahjat, R., Pine, P., Rus, V., & Tsokos, G. C. (2009). Differential expression and molecular associations of Syk in systemic lupus erythematosus T cells. Journal of Immunology, 181(11), 8145-8152. https://doi.org/10.4049/jimmunol.181.11.8145