Role of Syk in Tyrosine Phosphorylation Changes Associated with Redox Signaling in T Cells

Aims: reactive Oxygen Species (ROS) are important elements of the inflammatory process and are involved in cell signaling events. This work aims at assessing if redox stress can be sensed by T cells through protein thiol oxidation, eliciting tyrosine phosphorylation changes and specific cellular responses. Results: our data show that T cells respond to –SH groups oxidation with a distinctive tyrosine phosphorylation response. The release of T cell cytokines TNF, IFNγ and IL2 is affected by the oxidation. The expression of different receptors (CD69, CD62L, CD25, HLA-DR, CD45RA and CD45RO) is also affected in a specific way. Experiments with Syk inhibitors showed a major involvement of Syk. Importance: although previous reports have described an association between oxidative events and the modulation of innate immunity, the role of redox signaling in T cell mediated adaptive immunity is not well understood. This work shows the presence of a crosstalk between oxidation of cysteine residues and tyrosine phosphorylation changes, resulting in a series of functional events in T cells. Conclusions: our experiments demonstrate a link between cysteine oxidation and tyrosine phosphorylation changes in T cells and a novel role of Syk inhibitors in exerting their anti-inflammatory activity through the inhibition of a response initiated by ROS.