T cell tyrosine phosphorylation response to transient redox stress

• Published in: Cellular signalling 2015-04, Vol.27 (4), p.777-788
• Main Authors: Secchi, Christian, Carta, Marissa, Crescio, Claudia, Spano, Alessandra, Arras, Marcella, Caocci, Giovanni, Galimi, Francesco, La Nasa, Giorgio, Pippia, Proto, Turrini, Francesco, Pantaleo, Antonella
• Format: Article
• Language: English
• Subjects: Cysteine - immunology; Cysteine - metabolism; Cysteine oxidation; Humans; Immunity, Innate; Inflammation; Intracellular Signaling Peptides and Proteins - immunology; Intracellular Signaling Peptides and Proteins - metabolism; Jurkat Cells; Kinases & phosphatases; Oxidation-Reduction; Oxidative Stress; Phosphorylation; Protein-Tyrosine Kinases - immunology; Protein-Tyrosine Kinases - metabolism; Reactive Oxygen Species - immunology; Reactive Oxygen Species - metabolism; Syk inhibitors; Syk Kinase; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tyrosine - immunology; Tyrosine - metabolism; Tyrosine phosphorylation
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2014.12.014

Reactive Oxygen Species (ROS) are crucial to multiple biological processes involved in the pathophysiology of inflammation, and are also involved in redox signaling responses. Although previous reports have described an association between oxidative events and the modulation of innate immunity, a role for redox signaling in T cell mediated adaptive immunity has not been described yet. This work aims at assessing if T cells can sense redox stress through protein sulfhydryl oxidation and respond with tyrosine phosphorylation changes. Our data show that Jurkat T cells respond to –SH group oxidation with specific tyrosine phosphorylation events. The release of T cell cytokines TNF, IFNγ and IL2 as well as the expression of a number of receptors are affected by those changes. Additionally, experiments with spleen tyrosine kinase (Syk) inhibitors showed a major involvement of Syk in these responses. The experiments described herein show a link between cysteine oxidation and tyrosine phosphorylation changes in T cells, as well as a novel mechanism by which Syk inhibitors exert their anti-inflammatory activity through the inhibition of a response initiated by ROS.