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

Jennifer Ball, Isabella Vlisidou, Matthew Blunt, William Wood, Stephen Ward

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)3679-3689
Number of pages11
JournalThe Journal of Immunology
Volume198
Issue number9
Early online date17 Apr 2017
DOIs
Publication statusPublished - 1 May 2017

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Hydrogen Peroxide
T-Lymphocytes
Chemotaxis
src-Family Kinases
Chemokine Receptors
Adaptive Immunity
Phosphatidylinositol 3-Kinases
Cues
Actins
Oxidative Stress
Phosphorylation
Inflammation
Lipids
Wounds and Injuries

Cite this

Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration. / Ball, Jennifer; Vlisidou, Isabella; Blunt, Matthew; Wood, William; Ward, Stephen.

In: The Journal of Immunology, Vol. 198, No. 9, 01.05.2017, p. 3679-3689.

Research output: Contribution to journalArticle

Ball, Jennifer ; Vlisidou, Isabella ; Blunt, Matthew ; Wood, William ; Ward, Stephen. / Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration. In: The Journal of Immunology. 2017 ; Vol. 198, No. 9. pp. 3679-3689.
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