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

Frontiers in Immunology
Karina OyarceKarina Pino-Lagos

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 i...Continue Reading

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Citations

Feb 9, 2020·Journal of Leukocyte Biology·Christian PetersDieter Kabelitz
Mar 11, 2020·Frontiers in Immunology·Rebeca Arroyo HorneroMarkus Kleinewietfeld
Oct 18, 2020·European Journal of Immunology·Henry KurniawanDirk Brenner
Oct 13, 2020·Pharmacology & Therapeutics·Laura MasuelliRoberto Bei
Apr 20, 2021·Frontiers in Immunology·Julianna BlagihFabio Zani
Nov 26, 2021·Immunological Reviews·Heng-Yi ChenChan-Wang Jerry Lio

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Methods Mentioned

BETA
flow cytometry
Assay
PCR
ELISA
RNA-seq

Software Mentioned

FlowJo
GraphPad Prism

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