title: Redox regulation of the immune response.
abstract: Reactive oxygen and nitrogen species (ROS-RNS) and other redox active molecules fulfill key functions in immunity. Beside the initiation of cytocidal reactions within the pathogen defense strategy, redox reactions trigger and shape the immune response and are further involved in termination and initialization of cellular restorative processes. Regulatory mechanisms provided by redox-activated signaling events guarantee the correct spatial and temporal proceeding of immunological processes, and continued imbalances in redox homeostasis lead to crucial failures of control mechanisms, thus promoting the development of pathological conditions. Interferon-gamma is the most potent inducer of ROS-RNS formation in target cells like macrophages. Immune-regulatory pathways such as tryptophan breakdown via indoleamine 2,3-dioxygenase and neopterin production by GTP-cyclohydrolase-I are initiated during T helper cell type 1 (Th1-type) immune response concomitant to the production of ROS-RNS by immunocompetent cells. Therefore, increased neopterin production and tryptophan breakdown is representative of an activated cellular immune system and can be used for the in vivo and in vitro monitoring of oxidative stress. In parallel, the activation of the redox-sensitive transcription factor nuclear factor-kappa B is a central element in immunity leading to cell type and stimulus-specific expression of responsive genes. Furthermore, T cell activation and proliferation are strongly dependent on the redox potential of the extracellular microenvironment. T cell commitment to Th1, Th2, regulatory T cell, and other phenotypes appears to crucially depend on the activation of redox-sensitive signaling cascades, where oxidative conditions support Th1 development while 'antioxidative' stress leads to a shift to allergic Th2-type immune responses.
authors.affiliation: Division of Medical Biochemistry, Biocenter, Medical University, Innsbruck, Austria.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Gostner
authors.forename: Kathrin
authors.initials: K
authors.lastname: Becker
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Robert
authors.initials: R
authors.lastname: Sucher
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002454:Cell Differentiation; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D007109:Immunity / Q000502:physiology*; D007371:Interferon-gamma; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D010084:Oxidation-Reduction; D026361:Reactive Nitrogen Species / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000975:Antioxidants; D026361:Reactive Nitrogen Species; D007371:Interferon-gamma