The immune system protects the body from disease. It must also know when not to attack.
A special group of immune cells called regulatory T cells, or Tregs, helps maintain that balance. These cells prevent the immune system from attacking healthy tissues and organs.
Because of this unique role, researchers view Tregs as promising tools for treating autoimmune diseases and preventing transplant rejection.
Now, scientists at the La Jolla Institute for Immunology (LJI) and Emory University School of Medicine have identified a way to make laboratory-grown Tregs more stable and effective.
The research received partial support through a CIRM training grant.
Harnessing the Power of Regulatory T Cells
Tregs act as the immune system’s brakes.
They help prevent harmful immune responses that can damage healthy tissues.
When Tregs fail to function properly, the immune system may attack the body’s own cells. This process can lead to autoimmune diseases such as:
- Type 1 diabetes
- Multiple sclerosis
- Lupus
Tregs may also help address graft-versus-host disease (GvHD), a serious complication that can occur after bone marrow or stem cell transplantation.
In GvHD, transplanted immune cells attack the recipient’s tissues.
Researchers hope Treg-based therapies could help suppress these unwanted immune reactions.
How Vitamin C Helps Stabilize Immune Cells
Researchers led by Anjana Rao, PhD, at LJI and Benjamin Barwick, PhD, at Emory focused on developing stable induced regulatory T cells, known as iTregs.
Scientists create iTregs in the laboratory rather than collecting them directly from patients.
Previous studies suggested that vitamin C could enhance the activity of proteins called TET enzymes, which play an important role in regulating gene activity.
The team wanted to understand exactly how that process works.
Their findings showed that vitamin C and TET proteins work together to strengthen the identity and stability of iTregs.
Reprogramming How Cells Read DNA
The researchers examined both gene activity and changes in DNA structure.
They discovered that TET enzymes help modify DNA in ways that influence how cells interpret genetic information.
The team also observed changes in DNA accessibility.
DNA can exist in tightly packed or loosely organized forms. When DNA relaxes and opens up, regulatory regions become accessible and influence gene activity.
These changes help reinforce the genetic programs that allow iTregs to function properly.
By promoting these beneficial changes, vitamin C appeared to help stabilize the immune-regulating cells.
A Promising Future for Cell Therapy
The findings suggest a relatively simple strategy could improve the production of therapeutic Tregs.
“Vitamin C can be used to stabilize iTregs generated in vitro,” said LJI instructor Xiaojing Yue, PhD.
She added that these induced Tregs may eventually support treatments for autoimmune diseases and organ transplantation.
Researchers must complete additional studies before moving toward clinical applications. However, the results offer new insight into how scientists might improve cell-based therapies that regulate the immune system.
Looking Ahead
Treg therapies hold significant promise because they aim to restore balance rather than broadly suppress immune activity.
By improving the stability of laboratory-grown Tregs, researchers may move closer to developing new treatments for autoimmune diseases, transplant complications, and other immune-related conditions.
The study also highlights how a deeper understanding of gene regulation and cell biology can help scientists design more effective regenerative medicine therapies.
The findings were published in EMBO Reports.
During the development of most prokaryotes and eukaryotes, the pattern of DNA changes as a result of a dynamic process involving both de novo DNA methylation and demethylation, which have pivotal impact on genome stability, gene expression and development. DNA methylation regulates gene expression by inhibiting the binding of transcription factors into DNA and caused gene repression. Whereas, DNA demethylation occurs in replicating cells by preventing the addition of methyl groups to the DNA, so that replicated DNA will largely have cytosines in the DNA sequence. TET enzymes have important role to promote DNA demethylation through oxidize 5-methylcytosines lead to locus specific reversal of DNA methylation. TET family proteins are responsible for conversion of 5- methylcytosine to 5-hyroxymethylcytosune and consist of 3 members, namely TET1,TET2 and TET3. DNA methylation is vital modification process in the control of precise genetic expression and contributes to the epigenetic by regulating gene expression without changing DNA sequence. Both hypermethylation and hypomethylation are irregular changes in genetic methylation signal associated with many disorders and cancers. Nutrition affects the epigenetic regulation of DNA methylation in several possible epigenetic pathways. This is mainly by altering the substrates and cofactors that are necessary for proper DNA methylation ; addition by changing the activity of enzymes regulating the one-carbon cycle; lastly through diet modification in DNA methylation and demethylation. There are 2 types of risk factors can alter the epigenetic regulating of methylation pathways: genetic factors and modification factors. Nutrition is the strongest modifiable factors which has direct role in metabolize methyl groups in DNA methylation pathways. Therefore, nutrition is greatly influence gene expression and early nutrition alteration responsible for later development of chronic disease through epigenetic mechanism.
Current investigation showed that vitamin C plays key role as TET activator to enhance the expression of Treg signatures genes and epigenetic landscape of endogenous Treg cells. The evidence supported that vitamin C enhance IL-2 responsiveness, IL-2Rα expression, STAT5 phosphorylation and STAT5 binding. Thus, the ability of vitamin C to mimic and generate Treg-dependent IL-2/STAT5. It is important to determine whether vitamin C has similar enhancement features in other immune cells like Treg cells. The aim of experimental study is to develop the effective therapeutic approach by empowering the ability of Treg cells to function as suppressor cells in graf versus host disease and autoimmune diseases. It is interesting to exploit different kinds of analogs or vitamin C agonists which can selectively enhance Treg cells to function but not for other types of immunity.
There was a hot issue of one-man story happening in my home town. A man contracted with Covid-19 delta variant did not seek help for hospitalised. Almost all the hospitals are overwhelmed with Covid-19 patients. He took risk by taking a lot of fruits and vitamin C. Surprisingly, he was fully cured from Covid-19 symptoms. The vitamin C may probably have enhancement role in human’s immunity.