Regulatory T cells ( Tregs) help control autoimmunity and inflammation in the body. These cells are so important that scientists are working to generate stable induced Tregs in vitro for use as a rejection to transplanted organs and as treatments for autoimmune diseases. It has been not easy to find the right molecular ingredients to induce stable iTregs. Now from the US, a team of researchers has found that proteins of the TET family and Vitamin C can work together to give Tregs their life-saving power.
According to lead author Dr. Xiaojing Yue, a researcher in the Division of Signaling and Gene Expression at the La Jolla Institute for Immunology, “Vitamin C can be used to stabilize iTregs generated in vitro. We hope that these kinds of induced Tregs can be used in the future for the treatment of autoimmune diseases and organ transplantation.”
The current study builds on the earlier findings that vitamin C can prompt the generation of stable iTregs under lab conditions and enhance the enzymatic activity of TET proteins. Dr. Yue and colleagues did not want to work toward new autoimmune therapies without 1st analyzing the other key epigenetic features and gene expression patterns and of the induced Tregs.
Dr. Yue said, “We wanted to study the entire system at a whole-genome level using next-generation sequencing technology to better understand the molecular features of these cells.” In the major type of epigenetic modification, DNA itself is involved by removing or adding molecules called methyl groups from cytosines.
TET enzymes can further oxidize the methyl groups. How cells read the DNA code is changed by all of these interactions. Another type of epigenetic change involves altering DNA accessibility: whether DNA is loosely or tightly coiled. Regulatory regions become exposed as the DNA coils unwind, which subsequently influence gene expression.
Researchers in their analysis found that TET proteins are required and epigenetic features that make Tregs what they are for maintaining the gene expression. Vitamin C is added to iTregs with similar epigenetic features and gene expression as normal wild-type Tregs found in the body.
An intriguing connection the scientists also found between IL-2/STAT5 signaling, Vitamin C, and TET enzymatic activity. The researchers shared that TET deficiency in Treg cells leads to impaired IL-2/STAT5 signaling. Vitamin C confers iTregs enhanced IL-2/STAT5 signaling.