Regulatory T cells (Tregs) are a type of immune cell that play an extremely important role in maintaining stability in the body and preventing the body’s immune system from attacking its own cells and organs. This unique property makes Tregs extremely valuable to researchers as a potential treatment for immune related issues. One of these is autoimmune disease, which is a disease in which the body’s own immune system attacks healthy cells. Some examples of this are type 1 diabetes, multiple sclerosis, and lupus. Another immune related issue is graft vs. host disease (GvHD), which can occur after receiving a transplantation where the donated bone marrow or stem cells start attacking the recipient.
For this reason, researchers at the La Jolla Institute for Immunology (LJI) and Emory University School of Medicine, partially supported by a CIRM training grant , have been working to generate stable induced Tregs (iTregs) for treating autoimmune diseases and rejection of a transplanted organ. The teams were led by LJI professor Anjana Rao, Ph.D, and Emory instructor Benjamin G. Barwick, Ph.D. The two team study showed evidence that vitamin C and and specific proteins called TET can be combined to give Tregs their life-saving power. Studies have previously found that vitamin C can enhance the activity of TET proteins and prompt the generation of stable iTregs under lab conditions.
For this study, the researchers also analyzed gene expression patterns as well as changes that altered the physical structure of DNA in the induced Tregs. The team found a major modification involving the DNA itself and showed that TET enzymes were also involved. All of these interactions can eventually change how cells “read” the DNA code. They also observed the alteration of DNA accessibility which depends on whether DNA is loosely or tightly coiled. As the DNA coils unwind, regulatory regions become exposed which subsequently influence gene expression.
In a news release, LJI instructor Xiaojing Yue, Ph.D elaborated on the results of this study.
“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 treatment of autoimmune diseases and organ transplantation.”
The full study was published in EMBO reports.
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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.