Hydrogen peroxide triggers a dual signaling axis to selectively suppress activated human T lymphocyte migration

Ball, Jennifer A., Vlisidou, Isabella, Blunt, Matthew D., Wood, Will and Ward, Stephen G. (2017) Hydrogen peroxide triggers a dual signaling axis to selectively suppress activated human T lymphocyte migration. Journal of immunology (Baltimore, Md. : 1950), 198 (9), 3679–3689. (doi:10.4049/jimmunol.1600868).

Abstract

H₂O₂ is an early danger cue required for innate immune cell recruitment to wounds. To date, little is known about whether H₂O₂ is required for the migration of human adaptive immune cells to sites of inflammation. However, oxidative stress is known to impair T cell activity, induce actin stiffness, and inhibit cell polarization. In this study, we show that low oxidative concentrations of H₂O₂ also impede chemokinesis and chemotaxis of previously activated human T cells to CXCL11, but not CXCL10 or CXCL12. We show that this deficiency in migration is due to a reduction in inflammatory chemokine receptor CXCR3 surface expression and cellular activation of lipid phosphatase SHIP-1. We demonstrate that H₂O₂ acts through an Src kinase to activate a negative regulator of PI3K signaling, SHIP-1 via phosphorylation, providing a molecular mechanism for H₂O₂-induced chemotaxis deficiency. We hypothesize that although H₂O₂ serves as an early recruitment trigger for innate immune cells, it appears to operate as an inhibitor of T lymphocyte immune adaptive responses that are not required until later in the repair process.

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Contributors

Author: Matthew D. Blunt

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