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

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.

Mathematical Modelling and Computational Simulation of Mammalian Cell Cycle Progression in Batch Systems

“…The results shown represent only a limited portion of the potential of the proposed model which, nevertheless, needs specific experimental validation for demonstrating its full reliability and effective applicability. Work is underway to include for example the effect of cell cycle synchronization factors (Banfalvi, 2017;Pantaleo et al, 2017;Secchi et al, 2020). This aspect is of peculiar importance for infection with lentivirus (Trobridge and Russell, 2004;Bonfalvi, 2017;Pantaleo et al, 2017;Secchi et al, 2020) to generate GM cells, typically for mAb production (or any other recombinant protein).…”

“…Work is underway to include for example the effect of cell cycle synchronization factors (Banfalvi, 2017;Pantaleo et al, 2017;Secchi et al, 2020). This aspect is of peculiar importance for infection with lentivirus (Trobridge and Russell, 2004;Bonfalvi, 2017;Pantaleo et al, 2017;Secchi et al, 2020) to generate GM cells, typically for mAb production (or any other recombinant protein).…”

Invalidation of the Transcriptional Modulator of Lipid Metabolism PPARβ/δ in T Cells Prevents Age-Related Alteration of Body Composition and Loss of Endurance Capacity

“…It has been shown that the absence of CD25 in peripheral Tregs was determinant of their increased susceptibility to oxidative stress, mitochondrial dysfunction, and apoptosis and of the transcription of lipid and cholesterol biosynthetic key enzymes ( Toomer et al, 2019 ). Moreover, CD25 expression at the cell surface was dependent on a redox-regulated signaling pathway ( Secchi et al, 2020 ) and was decreased on Tregs from aged mice ( Chougnet et al, 2011 ). Taking all these data into account, since older KO-T PPARβ/δ mice display less FoxP3 + CD25 – cells (accompanied by a concomitant increase in FoxP3 + CD25 + cell proportion), one might expect that Tregs of these mice are preserved from the effects of aging and oxidative stress, and thus more functional and less prone to immunosenescence.…”

Stoichiometric Thiol Redox Proteomics for Quantifying Cellular Responses to Perturbations

“…From a structural perspective, as noted by Go and Jones, thiol redox modifications can be classified into four different types of switches that have a modulatory effect: on-off (protein in-/activation), interaction (binding), allosteric (regulates activity), and thiolation (alternate function) [ 44 ]. As some thiol-based redox modifications are reversible, this can permit rapid activation or inactivation of signaling pathways [ 45 ], leading to their transient activity [ 46 , 47 ]. One example is the transient receptor potential (TRP) family of Ca 2+ cation channels that are found in photoreceptors and other cell types.…”