title: 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.
authors.affiliation: College of Pharmacy, Division of Life and Pharmaceutical Sciences, and Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Korea.
authors.forename: Hee Yeon
authors.initials: HY
authors.lastname: Won
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Sohn
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Min
authors.forename: Kihyun
authors.initials: K
authors.lastname: Lee
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Woo
authors.forename: Ye-Shih
authors.initials: YS
authors.lastname: Ho
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Park
authors.forename: Sue-Goo
authors.initials: SG
authors.lastname: Rhee
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Hwang
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D017252:CD3 Complex / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D005979:Glutathione Peroxidase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020397:Goblet Cells / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D020825:T-Box Domain Proteins / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1; D000098815:T-bet Transcription Factor
chemical_list: D000485:Allergens; D000906:Antibodies; D000975:Antioxidants; D017252:CD3 Complex; D016207:Cytokines; D018398:Homeodomain Proteins; D007376:Interleukin-2; D017382:Reactive Oxygen Species; C484663:Shox2 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D003094:Collagen; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse