Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation.
Oxidative stress plays an important role in the pathogenesis of asthma via the upregulation of local inflammatory mediators and/or promoting Th2-skewing during Ag sensitization. Thioredoxin (TRX), a 12 kDa redox-active protein with antioxidative property, has been recently shown to play a protective role in various inflammatory diseases. Using a mouse model of asthma, we show here that IL-13 and eotaxin production are decreased in TRX-Tg mice leading to reduced eosinophils recruitment and mucus metaplasia. The reduction in airway inflammation occurs without the attenuation of systemic Th2 immunity in that comparable levels of Th2-type cytokines and Ig were detected in LN and serum, respectively, from TRX-Tg and WT mice. Likewise, CD4(+) T cells from both strains of mice developed similar Th1 and Th2 responses in vitro. Asthmatic lungs of TRX-Tg and WT mice contained similar amounts of GATA-3(+) and Foxp3(+) T cells. Finally, production of MIF, an upstream modulator of airway inflammation, was significantly reduced in the lungs of TRX-Tg mice. Our data suggest that TRX suppresses airway inflammation by inhibiting MIF production thereby limiting the downstream recruitment of eosinophils to the lung independently of modulating systemic Th1/Th2 immunity.
Torii
Mie
M
Department of Cellular and Molecular Immunology, Mie University Graduate School of Medicine, Tsu, Japan.
Wang
Linan
L
Ma
Ning
N
Saito
Kanako
K
Hori
Tomohide
T
Sato-Ueshima
Maremi
M
Koyama
Yoshikazu
Y
Nishikawa
Hiroyoshi
H
Katayama
Naoyuki
N
Mizoguchi
Akira
A
Shiku
Hiroshi
H
Yodoi
Junji
J
Kuribayashi
Kagemasa
K
Kato
Takuma
T
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D013879:Thioredoxins / Q000276:immunology*
D018793:Interleukin-13; D008263:Macrophage Migration-Inhibitory Factors; D013879:Thioredoxins; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse