Vitamin C fosters the in vivo differentiation of peripheral CD4+ Foxp3- T cells into CD4+ Foxp3+ regulatory T cells but impairs their ability to prolong skin allograft survival

Karina Oyarce, Mauricio Campos-Mora, Tania Gajardo-Carrasco, Karina Pino-Lagos

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Regulatory T cells (Tregs) are critical players of immunological tolerance due to their ability to suppress effector T cell function thereby preventing transplant rejection and autoimmune diseases. During allograft transplantation, increases of both Treg expansion and generation, as well as their stable function, are needed to ensure allograft acceptance; thus, efforts have been made to discover new molecules that enhance Treg-mediated tolerance and to uncover their mechanisms. Recently, vitamin C (VitC), known to regulate T cell maturation and dendritic cell-mediated T cell polarization, has gained attention as a relevant epigenetic remodeler able to enhance and stabilize the expression of the Treg master regulator gene Foxp3, positively affecting the generation of induced Tregs (iTregs). In this study, we measured VitC transporter (SVCT2) expression in different immune cell populations, finding Tregs as one of the cell subset with the highest levels of SVCT2 expression. Unexpectedly, we found that VitC treatment reduces the ability of natural Tregs to suppress effector T cell proliferation in vitro, while having an enhancer effect on TGFβ-induced Foxp3+ Tregs. On the other hand, VitC increases iTregs generation in vitro and in vivo, however, no allograft tolerance was achieved in animals orally treated with VitC. Lastly, Tregs isolated from the draining lymph nodes of VitC-treated and transplanted mice also showed impaired suppression capacity ex vivo. Our results indicate that VitC promotes the generation and expansion of Tregs, without exhibiting CD4+ T cell-mediated allograft tolerance. These observations highlight the relevance of the nutritional status of patients when immune regulation is needed.

Original languageEnglish
Article number112
JournalFrontiers in Immunology
Volume9
Issue numberFEB
DOIs
StatePublished - 9 Feb 2018

Bibliographical note

Funding Information:
This work was supported by FONDECYT Regular Grant 1160347 and FAI Postdoc UAndes. The authors are thankful to Carla ?lvarez (Universidad de Chile) for assisting in some in vitro experiments, to Dr. Coralia Rivas (Universidad de Concepci?n, Chile) for advising on VitC incorporation assays and to Petra Sergent for reading/correcting manuscript writing (Geisel School of Medicine at Dartmouth College, NH, USA)

Funding Information:
This work was supported by FONDECYT Regular Grant 1160347 and FAI Postdoc UAndes. The authors are thankful to Carla álvarez (Universidad de Chile) for assisting in some in vitro experiments, to Dr. Coralia Rivas (Universidad de Concepción, Chile) for advising on VitC incorporation assays and to Petra Sergent for reading/correcting manuscript writing (Geisel School of Medicine at Dartmouth College, NH, USA)

Publisher Copyright:
© 2018 Oyarce, Campos-Mora, Gajardo-Carrasco and Pino-Lagos.

Keywords

  • Foxp3
  • Regulatory T cells
  • Tolerance
  • Transplantation
  • Vitamin C

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