title: 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.
authors.affiliation: Department of Biomedical Sciences, University of Sassari, I-07100 Sassari, Italy; Istituto Nazionale Biostrutture e Biosistemi, University of Sassari, I-07100, Sassari, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Secchi
authors.affiliation: Department of Biomedical Sciences, University of Sassari, I-07100 Sassari, Italy.
authors.forename: Marissa
authors.initials: M
authors.lastname: Carta
authors.affiliation: Department of Biomedical Sciences, University of Sassari, I-07100 Sassari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Crescio
authors.affiliation: Department of Biomedical Sciences, University of Sassari, I-07100 Sassari, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Spano
authors.affiliation: Haematology, Hospital Binaghi, ASL 8 Cagliari, I-09126, Cagliari, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Arras
authors.affiliation: Haematology, Department of Medical Sciences, University of Cagliari, I-09042 Cagliari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Caocci
authors.affiliation: Department of Biomedical Sciences, University of Sassari, I-07100 Sassari, Italy; Istituto Nazionale Biostrutture e Biosistemi, University of Sassari, I-07100, Sassari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Galimi
authors.affiliation: Haematology, Department of Medical Sciences, University of Cagliari, I-09042 Cagliari, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: La Nasa
authors.affiliation: Department of Biomedical Sciences, University of Sassari, I-07100 Sassari, Italy.
authors.forename: Proto
authors.initials: P
authors.lastname: Pippia
authors.affiliation: Department of Genetics, Biology and Biochemistry, University of Turin, I-10126 Turin, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Turrini
authors.affiliation: Department of Biomedical Sciences, University of Sassari, I-07100 Sassari, Italy. Electronic address: apantaleo@uniss.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Pantaleo
mesh_terms: D003545:Cysteine / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine / Q000276:immunology / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D003545:Cysteine
keywords: Cysteine oxidation; Inflammation; Kinases & phosphatases; Syk inhibitors; T cells; Tyrosine phosphorylation