Glutathione peroxidase 1 deficiency attenuates allergen-induced airway inflammation by suppressing Th2 and Th17 cell development
- PMID: 20367278
- DOI: 10.1089/ars.2009.2989
Glutathione peroxidase 1 deficiency attenuates allergen-induced airway inflammation by suppressing Th2 and Th17 cell development
Abstract
Engagement of T cell receptor (TCR) triggers signaling pathways that mediate activation, proliferation, and differentiation of T lymphocytes. Such signaling events are mediated by reactive oxygen species (ROS), including hydrogen peroxide and lipid peroxides, both of which are reduced by glutathione peroxidase 1 (GPx1). We have now examined the role of GPx1 in the activation, differentiation, and functions of CD4(+) T helper (Th) cells. TCR stimulation increased the intracellular ROS concentration in Th cells in a time-dependent manner, and such TCR-induced ROS generation was found to promote cell proliferation. GPx1-deficient Th cells produced higher levels of intracellular ROS and interleukin-2 than wild-type Th cells and proliferated at a faster rate than did wild-type cells. Moreover, differentiation of GPx1-deficient Th cells was biased toward Th1, and Th17 cell development was also impeded by GPx1 depletion. Consistent with these findings, GPx1-null mice were protected from the development of ovalbumin-induced allergic asthma. Eosinophil infiltration, goblet cell hyperplasia, collagen deposition, and airway hyperresponsiveness were thus all attenuated in the lungs of GPx1-null mice. These data indicate that GPx1-dependent control of intracellular ROS accumulation is important not only for regulation of Th cell proliferation but for modulation of differentiation into Th1, Th2, and Th17 cells.
Comment in
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Different isoforms of glutathione peroxidase cause opposing effects during the development of allergic asthma in mice.Antioxid Redox Signal. 2011 Jan 1;14(1):169-70; author reply 170-1. doi: 10.1089/ars.2010.3591. Epub 2010 Nov 5. Antioxid Redox Signal. 2011. PMID: 20831447 No abstract available.
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