T cell tyrosine phosphorylation response to transient redox stress

Abstract

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.

Signaling Response to Transient Redox Stress in Human Isolated T Cells: Molecular Sensor Role of Syk Kinase and Functional Involvement of IL2 Receptor and L-Selectine

“…As described previously [59], we found a molecular and functional relationship between SH group oxidation and Tyr phosphorylation in Jurkat cells. We here investigated if this mechanism is maintained in purified primary T cells.…”

“…Its concentration was chosen to observe those changes avoiding cell toxicity. Experiments with purified human T cells were performed in order to clarify the phenomena observed with Jurkat T cell line [59]. After purification from healthy donor blood, T cells were treated with 0.3 mM diamide ( Figure 1).…”

“…Nevertheless, we published our findings on Jurkat T cells which respond to -SH group oxidation with specific tyrosine phosphorylation events. Experiments with spleen tyrosine kinase (Syk) inhibitors showed upstream participation of Syk in these responses [59].…”

Oxidative stress in multiple sclerosis: Central and peripheral mode of action

“…Today we know that ROS and redox states are both central to immunity and T-cell function. First, and maybe most importantly, T-cells can sense redox stress (Secchi et al, 2015). Furthermore, redox stress is important for the functional outcome during experimentally-induced adaptive-immunity responses; e.g.…”

Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections

“…In adults, oxidative stress plays a role in COPD disease progression (149). It is possible that changes in the oxidative state of the lung due to chronic oxygen exposure in preterm infants could change how cells from the immune system respond to environmental exposures by altering cellular function or the types of cytokines that are produced (150)(151)(152)(153). These cytokines could work in concert with cell types in the lung, including epithelial cells and innate lymphoid cells, known to produce pro-inflammatory and pro-fibrotic factors under certain conditions (154).…”