The role of Syk in peripheral T cells

Publication date: Available online 16 April 2018
Source:Clinical Immunology
Author(s): Jeoung-Eun Park, Sirshendu Majumdar, David D. Brand, Edward F. Rosloniec, Ae-Kyung Yi, John M. Stuart, Andrew H. Kang, Linda K. Myers
The aim of this study was to understand how Syk affects peripheral T cell function. T cells from Syk^−/− chimeric mice and DR1 Syk^fl/fl CD4^cre conditional mice gave strong CD3-induced Th1, Th2, and Th17 cytokine responses. However, an altered peptide ligand (APL) of human CII (256–276) with two substitutions (F263N, E266D), also called A12, elicited only Th2 cytokine responses from Syk^fl/fl T cells but not Syk^fl/fl-CD4^cre T cells. Western blots revealed a marked increase in the phosphorylation of Syk, JNK and p38 upon A12/DR1 activation in WT or Syk^fl/fl T cells but not in Syk^fl/flCD4^-cre cells. We demonstrate that Syk is required for the APL- induction of suppressive cytokines. Chemical Syk inhibitors blocked activation of GATA-3 by peptide A12/DR1. In conclusion, this study provides novel insights into the role that Syk plays in directing T cell activity, and may shape therapeutic approaches for autoimmune diseases.



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