27-Jul-2022 - Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH

How tiny changes help T cells survive

Essential function of m6A modifications in T cells revealed.

The chemical modification of nucleic acids, known as methylation, exists not only on DNA but also on RNA. So far, it is still unclear whether this methylation is important for certain cell types and what effects it has on the interaction of cells in the body. The most abundant modification on mRNA, the messenger RNA molecules, is the so-called N6-methyladenosine, or m6A for short. It appears to play a crucial role in cell differentiation and to influence a number of biological processes. In this process, a methyl group is attached to the sixth carbon atom of the nucleic base adenosine. A so-called writer complex decides which adenosine molecule in which mRNA is modified at all and thus carries new information in addition to the genetic code. This information is "read" by so-called reader proteins, which then decide whether and when an mRNA is translated into a protein.

A new success for basic research

Vigo Heissmeyer and his research team now investigated how the loss of m6A affects the biology of T cells. To do this, they knocked out a component of the m6A writer complex in mice in their study - both in regulatory T cells and naïve T cells. From past studies, the researchers deduced that m6A modifications are essential for T cells when they recognize an antigen. Normally, antigen recognition would lead to T cell activation, cell division, and acquisition of effector functions. Regulatory T cells lacking m6A would lose their control over the immune response. Naive cells, on the other hand, stop developing and go into a kind of coma - or so researchers thought. The new study shows something different for naive T cells: Genetic inactivation of m6A gene regulation enhances calcium signaling, hyperactivating T cells and triggering cell death. The lack of regulation in T cells due to loss of adenosine methylation shows a severe inflammatory response in mice. They suffer from chronic inflammatory bowel disease. This disease is triggered by an excess of activated conventional T cells. An imbalance occurs because the regulatory T cells can no longer thwart the activation of the naïve T cells. In the absence of m6A in T cells, a complex deregulation of the immune response occurs; naïve T cells are activated by antigen recognition, divide initially, but also die prolifically - and can still trigger the disease, presumably because of a lack of suppression by regulatory T cells.

The researchers' next step is to study the molecules that recognize methylation. "Our idea is to use our findings on gene regulation to define new key molecules of T cell activation. We can see from our study which mRNAs are modified and thus need to be precisely defined in quantity for immune responses to be error-free," says Vigo Heissmeyer. "When we fully understand how this regulation prevents cell death or overactivation, we will also know which nodes can be therapeutically manipulated."

Note: This article has been translated using a computer system without human intervention. LUMITOS offers these automatic translations to present a wider range of current news. Since this article has been translated with automatic translation, it is possible that it contains errors in vocabulary, syntax or grammar. The original article in German can be found here.

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH

Recommend news PDF version / Print Add news to watchlist

Share on

Facts, background information, dossiers

  • cells
  • adenosine
  • RNA
  • T cells

More about Helmholtz Zentrum München

  • News

    The oat genome unlocks the unique health benefits of oats

    Researchers have succeeded in sequencing and characterizing the entire genome of oat. Compared to other cereals and humans, the oat genome architecture is very complex. Scientists from Helmholtz Munich, Lund University and the ScanOats network finally elucidated at the genetic level why oat ... more

    A Speed Limit Could Be a Breakthrough for Stem Cell Therapy

    Replacing sick or damaged cells with healthy cells: this is a major goal of regenerative medicine. One of the most promising approaches is cellular reprogramming, whereby one cell type in our body converts to another cell type. Research carried out at Helmholtz Munich and Ludwig-Maximilians ... more

    COVID-19: Breakthrough infection can substitute for a third vaccine shot

    According to a new study led by Ulrike Protzer, a breakthrough infection after two vaccinations achieves the same protective effect as an additional booster vaccination. According to the study by Helmholtz Munich, LMU and TUM, the decisive factor for immunity is that the immune system has h ... more

  • q&more articles

    Using deep learning to better understand blood disorders

    For a long time, doctors have been diagnosing disorders of the body’s hematopoietic system using a light microscope. The analysis of individual blood cells is largely performed manually. Now, artificial intelligence can lend them a digital hand. more

  • Authors

    Dr. Carsten Marr

    Carsten Marr, born in 1977, received his diploma in general physics from the Technische Universität München in 2002. He wrote his diploma thesis at the Max-Planck-Institute for Quantum Optics, Garching, Germany, and in 2003 visited the Quantum Information and Quantum Optics Theory Group at ... more

    Dr. Christian Matek

    Christian Matek, born in 1986, received undergraduate degrees in both Physics and Medicine in Munich. He then moved to the UK and finished his DPhil in Theoretical Physics at Oxford University in 2014. Since 2017, his main research interest has been applying artificial intelligence and mach ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: