Alloantigen-Induced Regulatory T Cells Generated in Presence of Vitamin C Display Enhanced Stability of Foxp3 Expression and Promote Skin Allograft Acceptance
Regulatory T cells (Tregs) are critical for the maintenance of immune homeostasis and self-tolerance and can be therapeutically used for prevention of unwanted immune responses such as allotransplant rejection. Tregs are characterized by expression of the transcription factor Foxp3, and recent work...
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00748/full |
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| author | Eirini Nikolouli Matthias Hardtke-Wolenski Martin Hapke Michael Beckstette Robert Geffers Stefan Floess Elmar Jaeckel Jochen Huehn |
| author_facet | Eirini Nikolouli Matthias Hardtke-Wolenski Martin Hapke Michael Beckstette Robert Geffers Stefan Floess Elmar Jaeckel Jochen Huehn |
| author_sort | Eirini Nikolouli |
| collection | DOAJ |
| description | Regulatory T cells (Tregs) are critical for the maintenance of immune homeostasis and self-tolerance and can be therapeutically used for prevention of unwanted immune responses such as allotransplant rejection. Tregs are characterized by expression of the transcription factor Foxp3, and recent work suggests that epigenetic imprinting of Foxp3 and other Treg-specific epigenetic signatures genes is crucial for the stabilization of both Foxp3 expression and immunosuppressive properties within Tregs. Lately, vitamin C was reported to enhance the activity of enzymes of the ten-eleven translocation family, thereby fostering the demethylation of Foxp3 and other Treg-specific epigenetic signatures genes in developing Tregs. Here, we in vitro generated alloantigen-induced Foxp3+ Tregs (allo-iTregs) in presence of vitamin C. Although vitamin C hardly influenced the transcriptome of allo-iTregs as revealed by RNA-seq, those vitamin C-treated allo-iTregs showed a more pronounced demethylation of Foxp3 and other Treg-specific epigenetic signatures genes accompanied with an enhanced stability of Foxp3 expression. Accordingly, when being tested in vivo in an allogeneic skin transplantation model, vitamin C-treated allo-iTregs showed a superior suppressive capacity. Together, our results pave the way for the establishment of novel protocols for the in vitro generation of alloantigen-induced Foxp3+ Tregs for therapeutic use in transplantation medicine. |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T17:17:42Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-e2410dd6c2494dba94917c70593b285e2022-12-21T18:18:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-06-01810.3389/fimmu.2017.00748280409Alloantigen-Induced Regulatory T Cells Generated in Presence of Vitamin C Display Enhanced Stability of Foxp3 Expression and Promote Skin Allograft AcceptanceEirini Nikolouli0Matthias Hardtke-Wolenski1Martin Hapke2Michael Beckstette3Robert Geffers4Stefan Floess5Elmar Jaeckel6Jochen Huehn7Department Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment Gastroenterology, Hepatology, Endocrinology, Hannover Medical School, Hannover, GermanyDepartment Gastroenterology, Hepatology, Endocrinology, Hannover Medical School, Hannover, GermanyDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyGenome Analytics, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment Gastroenterology, Hepatology, Endocrinology, Hannover Medical School, Hannover, GermanyDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyRegulatory T cells (Tregs) are critical for the maintenance of immune homeostasis and self-tolerance and can be therapeutically used for prevention of unwanted immune responses such as allotransplant rejection. Tregs are characterized by expression of the transcription factor Foxp3, and recent work suggests that epigenetic imprinting of Foxp3 and other Treg-specific epigenetic signatures genes is crucial for the stabilization of both Foxp3 expression and immunosuppressive properties within Tregs. Lately, vitamin C was reported to enhance the activity of enzymes of the ten-eleven translocation family, thereby fostering the demethylation of Foxp3 and other Treg-specific epigenetic signatures genes in developing Tregs. Here, we in vitro generated alloantigen-induced Foxp3+ Tregs (allo-iTregs) in presence of vitamin C. Although vitamin C hardly influenced the transcriptome of allo-iTregs as revealed by RNA-seq, those vitamin C-treated allo-iTregs showed a more pronounced demethylation of Foxp3 and other Treg-specific epigenetic signatures genes accompanied with an enhanced stability of Foxp3 expression. Accordingly, when being tested in vivo in an allogeneic skin transplantation model, vitamin C-treated allo-iTregs showed a superior suppressive capacity. Together, our results pave the way for the establishment of novel protocols for the in vitro generation of alloantigen-induced Foxp3+ Tregs for therapeutic use in transplantation medicine.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00748/fullallo-iTregsFoxp3vitamin Cdemethylationtransplantation |
| spellingShingle | Eirini Nikolouli Matthias Hardtke-Wolenski Martin Hapke Michael Beckstette Robert Geffers Stefan Floess Elmar Jaeckel Jochen Huehn Alloantigen-Induced Regulatory T Cells Generated in Presence of Vitamin C Display Enhanced Stability of Foxp3 Expression and Promote Skin Allograft Acceptance Frontiers in Immunology allo-iTregs Foxp3 vitamin C demethylation transplantation |
| title | Alloantigen-Induced Regulatory T Cells Generated in Presence of Vitamin C Display Enhanced Stability of Foxp3 Expression and Promote Skin Allograft Acceptance |
| title_full | Alloantigen-Induced Regulatory T Cells Generated in Presence of Vitamin C Display Enhanced Stability of Foxp3 Expression and Promote Skin Allograft Acceptance |
| title_fullStr | Alloantigen-Induced Regulatory T Cells Generated in Presence of Vitamin C Display Enhanced Stability of Foxp3 Expression and Promote Skin Allograft Acceptance |
| title_full_unstemmed | Alloantigen-Induced Regulatory T Cells Generated in Presence of Vitamin C Display Enhanced Stability of Foxp3 Expression and Promote Skin Allograft Acceptance |
| title_short | Alloantigen-Induced Regulatory T Cells Generated in Presence of Vitamin C Display Enhanced Stability of Foxp3 Expression and Promote Skin Allograft Acceptance |
| title_sort | alloantigen induced regulatory t cells generated in presence of vitamin c display enhanced stability of foxp3 expression and promote skin allograft acceptance |
| topic | allo-iTregs Foxp3 vitamin C demethylation transplantation |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00748/full |
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