Glutathione peroxidase 1 deficiency attenuates allergen-induced airway inflammation by suppressing th2 and th17 cell development

Hee Yeon Won, Jung Ho Sohn, Hyun Jung Min, Kihyun Lee, Hyun Ae Woo, Ye Shih Ho, Jung Won Park, Sue Goo Rhee, Eun Sook Hwang

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)575-587
Number of pages13
JournalAntioxidants and Redox Signaling
Volume13
Issue number5
DOIs
Publication statusPublished - 2010 Sep 1

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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