Abstract
Reactive oxygen species (ROS) are central effectors of inflammation and play a key role in cell signaling. Previous reports have described an association between oxidative events and the modulation of innate immunity. However, the role of redox signaling in adaptive immunity is still not well understood. This work is based on a novel investigation of diamide, a specific oxidant of sulfhydryl groups, and it is the first performed in purified T cell tyrosine phosphorylation signaling. Our data show that ex vivo T cells respond to –SH group oxidation with a distinctive tyrosine phosphorylation response and that these events elicit specific cellular responses. The expression of two essential T-cell receptors, CD25 and CD62L, and T-cell cytokine release is also affected in a specific way. Experiments with Syk inhibitors indicate a major contribution of this kinase in these phenomena. This pilot work confirms the presence of crosstalk between oxidation of cysteine residues and tyrosine phosphorylation changes, resulting in a series of functional events in freshly isolated T cells. Our experiments show a novel role of Syk inhibitors in applying their anti-inflammatory action through the inhibition of a ROS-generated reaction.
Highlights
reactive oxygen species (ROS) have been known as markers of cellular stress for long time
Our findings showed that spleen tyrosine kinase (Syk) inhibitors can stop the response initiated by ROS implying that their anti-inflammatory action involves adaptive immunity via T-cell modulation
T cells after isolation had a high rate of purity (99%) as showed in Supplemental Figure S2
Summary
ROS have been known as markers of cellular stress for long time. they can act as second messengers in the intracellular signaling and can potentially activate and control a multiplicity of function in different cell type [1,2,3,4,5]. Studies on erythrocyte membrane stability [18,19,20] revealed that oxidation induces a phosphorylation response that involves 2 tyrosine residues located in the cytoplasmic domain of band 3 protein. Published reports are focused on the notion that the major targets of ROS involve protein tyrosine phosphatases (PTPs) and the oxidation of their cys residues provoking their activity inhibition [57,58]. We report for the first time an ex vivo study on isolated T cells from healthy donors aimed to monitor the phosphorylation response to a temporary redox stress induced by diamide in the presence or absence of Syk Inhibitors (Figure 1). Our findings showed that Syk inhibitors can stop the response initiated by ROS implying that their anti-inflammatory action involves adaptive immunity via T-cell modulation
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