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Front Immunol. 2018 Nov 14;9:2584. doi: 10.3389/fimmu.2018.02584. eCollection 2018.

Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione.

Author information

1
Section Molecular Immunology, Institute of Immunology, Heidelberg University, Heidelberg, Germany.
2
Division of Rheumatology, Department of Internal Medicine V, Heidelberg University, Heidelberg, Germany.
3
Department of Human Molecular Genetics, Heidelberg University, Heidelberg, Germany.
4
nCounter Core Facility, Department of Human Molecular Genetics, Heidelberg University, Heidelberg, Germany.

Abstract

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. 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 downregulated the expression of the transcription factor RORγt, and 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 exogenously supplied GSH and by the GSH replenishing antioxidant N-acetylcysteine (NAC). Together, our study provides mechanistic insights into the mode of action of the natural substance SFN. 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.

KEYWORDS:

TH17; glutathione; primary human T-cells; reactive oxygen species; rheumatoid arthritis; sulforaphane

PMID:
30487791
PMCID:
PMC6246742
DOI:
10.3389/fimmu.2018.02584
[Indexed for MEDLINE]
Free PMC Article

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