Immune memory research could lead to the next generation of epigenetic drugs

A research team has discovered that immune system memory relies on distinctive epigenetic features and specific 3D arrangements of DNA in the nucleus of memory cells, which allow for rapid activation of these cells.

These features are altered in chronic inflammatory diseases such as asthma and may be important in autoimmune diseases and cancer.

The research team consisted of scientists from Erasmus University Medical Center in the Netherlands, and the Center for Genomic Regulation (CRG) and the Josep Carreras Leukemia Research Institute, both in Spain.

The immune system is one of the most complex parts of our body. It keeps us healthy by getting rid of parasites, viruses or bacteria, and by destroying damaged or cancerous cells. One of its most interesting capabilities is its memory: after the first contact with a foreign component (antigen), our adaptive immune system takes about two weeks to respond, but the response thereafter is much more rapid, as if the cell “remembered” the antigen.

But how is this memory obtained?

In a recent publication, a research team, coordinated by Ralph Stadhouders, from Erasmus MC, and Gregoire Stik, group leader at the Josep Carreras Leukemia Research Institute, provide new clues about immune memory.

Compare immune cell responses

In their research paper, published in the journal Science Immunology, first author Anne Onrust-van Schoonhoven and colleagues compared the response of immune cells that had never been in contact with an antigen (called naïve cells) to those of cells that had previously been exposed to an antigen. memory cells). They focused on differences in the epigenetic control of cellular machinery and cell nuclear architecture, two mechanisms that may explain the patterns of rapid activation of memory cells.

While all cells in an individual have the same genetic information, different cell types access different sections of DNA. The term “epigenetics” includes the mechanisms that dynamically control this access. The research team’s results revealed specific epigenetic marks in memory cells, resulting in rapid activation of an important set of genes compared to naïve cells.

These genes are much more accessible to cellular machinery, in particular the family of transcription factors called AP-1.

However, these epigenetic marks are only the tip of the iceberg. It is known that the position of DNA in the nucleus is not random and reflects the activation state of the cell. The researchers found that the 3D distribution of DNA in the nucleus differed between naïve and memory immune cells. Key genes for the initial immune response are grouped together and under the influence of the same regulatory regions, which are called enhancers.

Although most of the research has focused on healthy cells, the scientific team wondered whether whatever mechanisms discovered could, when altered, explain actual disease in which the immune system plays a critical role. To answer this question, they analyzed immune cells from chronic asthma patients and found that the circuits identified as key to an early and strong immune response were overactive.

Epigenetic control of the immune system is a growing field and discoveries like those by Stik and colleagues are setting the stage for the next generation of epigenetic drugs and treatments, which target autoimmune diseases and cancer.