Secrets of regulatory T cell development reveal clinical possibilities

A micrograph of a human T cell. Credit: NIAID

St. Jude Children's Research Hospital has identified biochemical "switches" that control the development of regulatory T cells and offer a novel strategy for treatment of autoimmune diseases and cancer. The journal Cell Reports published the research.

Significant progress has been made in understanding regulatory T cell development and function. The results come amid intense interest in the immune cells. Regulatory T cells help to maintain and fine-tune immune balance, which is key for preventing autoimmune diseases or enhancing cancer treatment.

The work defines how regulatory T cells come to act as immune suppressors and knits observations into a coherent understanding of the process. Practical guidance for future clinical trials is offered by this new model.

The process is three steps.

The Foxp3 was the focus of the research. Scientists knew Foxp3 was needed to turn immune cells into regulatory T cells. Knowledge about how Foxp3 expression was controlled was limited.

Researchers identified a three-step biochemical process while working in mouse T cells. The steps to starting an engine were compared by Feng.

The first step is to initiate regulatory T cell development.

The switch that turns on Foxp3 expression is similar to a battery starting an engine. Adding a chemical tag to histone acetylation promotes expression of the Foxp3 gene.

Fuel keeps an engine running, so another epigenetic process called DNA demethylation takes over to keep Foxp3 expression going. The chemical tag is removed from the DNA. Histone acetylation is no longer necessary once DNA demethylation begins.

The researchers reported that butyrate and vitamins C and C enhanced Foxp3 expression. They act at different steps in the process.

There is potential for clinical potential.

The study asked fundamental questions about how regulatory T cells are made. Understanding the basics will help people manipulate these cells in the future to treat diseases.

He said that the research revealed mechanisms that could be targeted to increase or decrease the number of regulatory T cells.

Jun Li and his team at Cell Reports have more information on Foxp3 maintenance and histone acetylation. Thecelrep.2021.110124 is published in the journal.

Cell reports are in the journal.

There are secrets of regulatory T cell development that reveal clinical possibilities.

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