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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02584/full |
| _version_ | 1819276504398299136 |
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| author | Jie Liang Beate Jahraus Emre Balta Jacqueline D. Ziegler Katrin Hübner Norbert Blank Beate Niesler Beate Niesler Guido H. Wabnitz Yvonne Samstag |
| author_facet | Jie Liang Beate Jahraus Emre Balta Jacqueline D. Ziegler Katrin Hübner Norbert Blank Beate Niesler Beate Niesler Guido H. Wabnitz Yvonne Samstag |
| author_sort | Jie Liang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T23:41:16Z |
| format | Article |
| id | doaj.art-700470e0cd0d4114b38c8c3c22e5373e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T23:41:16Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-700470e0cd0d4114b38c8c3c22e5373e2022-12-21T17:25:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02584408762Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting GlutathioneJie Liang0Beate Jahraus1Emre Balta2Jacqueline D. Ziegler3Katrin Hübner4Norbert Blank5Beate Niesler6Beate Niesler7Guido H. Wabnitz8Yvonne Samstag9Section Molecular Immunology, Institute of Immunology, Heidelberg University, Heidelberg, GermanySection Molecular Immunology, Institute of Immunology, Heidelberg University, Heidelberg, GermanySection Molecular Immunology, Institute of Immunology, Heidelberg University, Heidelberg, GermanySection Molecular Immunology, Institute of Immunology, Heidelberg University, Heidelberg, GermanySection Molecular Immunology, Institute of Immunology, Heidelberg University, Heidelberg, GermanyDivision of Rheumatology, Department of Internal Medicine V, Heidelberg University, Heidelberg, GermanyDepartment of Human Molecular Genetics, Heidelberg University, Heidelberg, GermanynCounter Core Facility, Department of Human Molecular Genetics, Heidelberg University, Heidelberg, GermanySection Molecular Immunology, Institute of Immunology, Heidelberg University, Heidelberg, GermanySection Molecular Immunology, Institute of Immunology, Heidelberg University, Heidelberg, GermanyThe 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.02584/fullsulforaphaneprimary human T-cellsreactive oxygen speciesglutathioneTH17rheumatoid arthritis |
| spellingShingle | Jie Liang Beate Jahraus Emre Balta Jacqueline D. Ziegler Katrin Hübner Norbert Blank Beate Niesler Beate Niesler Guido H. Wabnitz Yvonne Samstag Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione Frontiers in Immunology sulforaphane primary human T-cells reactive oxygen species glutathione TH17 rheumatoid arthritis |
| title | Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione |
| title_full | Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione |
| title_fullStr | Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione |
| title_full_unstemmed | Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione |
| title_short | Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione |
| title_sort | sulforaphane inhibits inflammatory responses of primary human t cells by increasing ros and depleting glutathione |
| topic | sulforaphane primary human T-cells reactive oxygen species glutathione TH17 rheumatoid arthritis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02584/full |
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