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Sulforaphane inhibits inflammatory responses of primary human T-cells by increasing ROS and depleting glutathione

The activity and function of T-cells are influenced by the intra- and extracellular redox milieu. Oxidative stress induces hypo-responsiveness of untransformed T-cells. Vice versa increased glutathione (GSH) levels or decreased levels of reactive oxygen species (ROS) prime T-cell metabolism for infl...

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Main Authors: Liang, Jie (Author) , Jahraus, Beate (Author) , Balta, Emre (Author) , Ziegler, Jacqueline D. (Author) , Hübner, Katrin (Author) , Blank, Norbert (Author) , Niesler, Beate (Author) , Wabnitz, Guido H. (Author) , Samstag, Yvonne (Author)
Format: Article (Journal)
Language:English
Published: 14 November 2018
In: Frontiers in immunology
Year: 2018, Volume: 9
ISSN:1664-3224
DOI:10.3389/fimmu.2018.02584
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.3389/fimmu.2018.02584
Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2018.02584/full
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Author Notes:Jie Liang, Beate Jahraus, Emre Balta, Jacqueline D. Ziegler, Katrin Hübner, Norbert Blank, Beate Niesler, Guido H. Wabnitz and Yvonne Samstag
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Summary:The activity and function of T-cells are influenced by the intra- and extracellular redox milieu. Oxidative stress induces hypo-responsiveness of untransformed T-cells. Vice versa increased glutathione (GSH) levels or decreased levels of reactive oxygen species (ROS) prime T-cell metabolism for inflammation, e.g. in rheumatoid arthritis (RA). Therefore, balancing the T-cell redox milieu may represent a promising new option for therapeutic immune modulation. Here we show that sulforaphane (SFN), a compound derived from plants of the Brassicaceae family, e.g. broccoli, induces a pro-oxidative state in untransformed human T-cells of healthy donors or RA patients. This manifested as an increase of intracellular ROS and a marked decrease of GSH. Consistently, increased global cysteine sulfenylation was detected. Importantly, a major target for SFN-mediated protein oxidation was STAT3, a transcription factor involved in the regulation of TH17-related genes. Accordingly, SFN significantly inhibited the activation of untransformed human T-cells derived from healthy donors or RA patients, and specifically downregulated the the transcription factor RORt expression of the TH17-related cytokines IL-17A, IL-17F, and IL-22, which play a major role within the pathophysiology of many chronic inflammatory/autoimmune diseases. The inhibitory effects of SFN could be abolished by exogenous supplied GSH and the GSH replenishing antioxidant N-acetyl-cysteine (NAC). Together, our study provides mechanistic insights into the mode of action of the natural substance sulforaphane. It specifically exerts TH17 prone immunosuppressive effects on untransformed human T-cells by decreasing GSH and accumulation of ROS. Thus, SFN may offer novel clinical options for the treatment of TH17 related chronic inflammatory/autoimmune diseases such as rheumatoid arthritis.
Item Description:Gesehen am 06.12.2018
Physical Description:Online Resource
ISSN:1664-3224
DOI:10.3389/fimmu.2018.02584

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