Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration

Jennifer A. Ball, Isabella Vlisidou, Matthew D. Blunt, Will Wood, Stephen G. Ward

Research output: Contribution to journalArticle (Academic Journal)peer-review

4 Citations (Scopus)
267 Downloads (Pure)

Abstract

Hydrogen peroxide (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 polarisation. Here, 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 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 a Src kinase to activate a negative regulator of PI3K signalling, SHIP-1 via phosphorylation providing a molecular mechanism for H2O2 induced chemotaxis deficiency. We hypothesise 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.
Original languageEnglish
Pages (from-to)3679-3689
Number of pages11
JournalJournal of Immunology
Volume198
Issue number9
Early online date31 Mar 2017
DOIs
Publication statusPublished - 1 May 2017

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