| Literature DB >> 29673901 |
Jeoung-Eun Park1, Sirshendu Majumdar1, David D Brand2, Edward F Rosloniec3, Ae-Kyung Yi4, John M Stuart3, Andrew H Kang3, Linda K Myers5.
Abstract
The aim of this study was to understand how Syk affects peripheral T cell function. T cells from Syk-/- chimeric mice and DR1 Sykfl/fl CD4cre 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 Sykfl/fl T cells but not Sykfl/fl-CD4cre T cells. Western blots revealed a marked increase in the phosphorylation of Syk, JNK and p38 upon A12/DR1 activation in WT or Sykfl/fl T cells but not in Sykfl/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.Entities:
Mesh：
Substances：
Year: 2018 PMID： 29673901 PMCID： PMC6350940 DOI： 10.1016/j.clim.2018.04.007
Source DB: PubMed Journal: Clin Immunol ISSN： 1521-6616 Impact factor: 3.969