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Intracellular glutathione redox status in human dendritic cells regulates IL-27 production and T-cell polarization


  • Edited by: Thomas Bieber

Dr Mitsuyoshi Utsugi, Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Tel.: +81 27 220 8123
Fax: +81 27 220 8136


To cite this article: Kamide Y, Utsugi M, Dobashi K, Ono A, Ishizuka T, Hisada T, Koga Y, Uno K, Hamuro J, Mori M. Intracellular glutathione redox status in human dendritic cells regulates IL-27 production and T-cell polarization. Allergy 2011; 66: 1183–1192.


Background:  Glutathione redox status, changes in intracellular reduced (GSH) or oxidized (GSSG) glutathione, plays a significant role in various aspects of cellular function. In this study, we examined whether intracellular glutathione redox status in human dendritic cells (DCs) regulates the polarization of Th1/Th2 balance.

Methods:  Human monocyte-derived DCs (MD-DCs) treated with glutathione reduced form ethyl ester (GSH-OEt) or L-buthionine-(S,R)-sulfoximine (BSO) were stimulated by lipopolysaccharide (LPS), and the levels of polarization cytokines were measured. Next, DCs matured by LPS or thymic stromal lymphopoietin (TSLP) were cocultured with allogeneic CD4+ naive T cells and Th1/Th2 balance was evaluated by cytokine production from the primed T cells.

Results:  Monocyte-derived DCs exposed to GSH-OEt and BSO had increased and decreased intracellular GSH contents, respectively. Lipopolysaccharide-induced interleukin (IL)-27 production was enhanced by GSH-OEt and suppressed by BSO, but neither GSH-OEt nor BSO affected the expression of HLA-DR, CD80, CD83, or CD86. Mature GSH-OEt-treated MD-DCs enhanced interferon (IFN)-γ production from CD4+ T cells compared with nontreated MD-DCs, and small interfering RNA (siRNA) against IL-27 suppressed the effect of GSH-OEt on IFN-γ production. Additionally, although human myeloid DCs activated by TSLP (TSLP-DCs) prime naïve CD4+ T cells to differentiate into Th2 cells, treatment of TSLP-DCs with GSH-OEt reduced IL-13 production and enhanced IFN-γ production by CD4+ T cells. Interleukin-27 siRNA attenuated the inhibitory effect of GSH-OEt on Th2 polarization.

Conclusion:  Our results reveal that Th1 and Th2 responses are controlled by intracellular glutathione redox status in DCs through IL-27 production.