The role of Syk in peripheral T cells

Jeoung-Eun Park; Sirshendu Majumdar; David D Brand; Edward F Rosloniec; Ae-Kyung Yi; John M Stuart; Andrew H Kang; Linda K Myers

doi:10.1016/j.clim.2018.04.007

The role of Syk in peripheral T cells

Clin Immunol. 2018 Jul:192:50-57. doi: 10.1016/j.clim.2018.04.007. Epub 2018 Apr 16.

Authors

Jeoung-Eun Park¹, Sirshendu Majumdar¹, David D Brand², Edward F Rosloniec³, Ae-Kyung Yi⁴, John M Stuart³, Andrew H Kang³, Linda K Myers⁵

Affiliations

¹ Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, United States.
² Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, United States; Microbiology-Immunology-Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, United States; Research Service, Veterans Affairs Medical Center, Memphis, TN 38104, United States.
³ Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, United States; Research Service, Veterans Affairs Medical Center, Memphis, TN 38104, United States.
⁴ Microbiology-Immunology-Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, United States.
⁵ Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, United States. Electronic address: lmyers@uthsc.edu.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Collagen Type II / genetics
Collagen Type II / immunology
Collagen Type II / metabolism
Cytokines / immunology
Cytokines / metabolism
GATA3 Transcription Factor / genetics
GATA3 Transcription Factor / immunology
GATA3 Transcription Factor / metabolism
Humans
Lymphocyte Activation / drug effects
Lymphocyte Activation / immunology*
Mice, Inbred DBA
Mice, Knockout
Mice, Transgenic
Peptides / immunology
Peptides / metabolism
Peptides / pharmacology
Phosphorylation
Protein-Tyrosine Kinases / pharmacology
Signal Transduction / drug effects
Signal Transduction / immunology*
Stilbenes / pharmacology
Syk Kinase / antagonists & inhibitors
Syk Kinase / genetics
Syk Kinase / immunology*
T-Lymphocytes / enzymology
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism
Th2 Cells / immunology
Th2 Cells / metabolism

Substances

Collagen Type II
Cytokines
GATA3 Transcription Factor
Peptides
Stilbenes
3,3',4,5'-tetrahydroxystilbene
Protein-Tyrosine Kinases
Syk Kinase

Abstract

Publication types

MeSH terms

Substances

Grants and funding