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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Bibliographic Details
Published in:Frontiers in immunology 2017-06, Vol.8, p.748-748
Main Authors: Nikolouli, Eirini, Hardtke-Wolenski, Matthias, Hapke, Martin, Beckstette, Michael, Geffers, Robert, Floess, Stefan, Jaeckel, Elmar, Huehn, Jochen
Format: Article
Language:English
Subjects:
allo-iTregs
demethylation
Foxp3
Immunology
transplantation
vitamin C
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Summary: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 and other Treg-specific epigenetic signatures genes is crucial for the stabilization of both 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 and other Treg-specific epigenetic signatures genes in developing Tregs. Here, we 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 and other Treg-specific epigenetic signatures genes accompanied with an enhanced stability of expression. Accordingly, when being tested 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 generation of alloantigen-induced Foxp3 Tregs for therapeutic use in transplantation medicine.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2017.00748