Integrative epigenome analyses uncover IL1RN promoter as a top DNAm-expression correlated event during myeloid cell commitment. Credit: Science Advances (2025). DOI: 10.1126/sciadv.adt1644

Controlling the activity of specific genes in the laboratory through the editing of their epigenetic marks is now a reality thanks to the CRISPR technology. A team from the Josep Carreras Leukemia Research Institute has demonstrated that it is possible to precisely control the methylation status of one of the key genes involved in controlling the inflammatory response (IL1RN), thereby modifying how the cell responds to external stimuli. With this finding, the development of innovative therapies based on epigenome editing to tackle inflammatory diseases, including myeloid leukemia, is one step closer.

Genes, fragments of DNA located on our chromosomes, control much of what happens in cells. Each cell activates only the genes it needs, silencing the rest through molecular "switches" present on each gene. However, these switches can sometimes be erroneously activated, leading the cell to behave abnormally and potentially resulting in diseases such as cancer or autoimmune disorders.

The activity of these "switches" is regulated by their methylation status, chemical marks that can be added to or removed from DNA. Thanks to new tools based on CRISPR-Cas9 technology, the team led by Dr. José Luis Sardina, group leader at the Josep Carreras Institute, has succeeded in controlling the "switch" of the IL1RN gene in cells derived from human leukemia, turning it on or off by adding or removing these chemical marks.

The results of the study, led by Dr. Gemma Valcárcel and conducted in collaboration with Dr. Esteban Ballestar's team, have just been published in the journal Science Advances. The research demonstrates how precise control of IL1RN gene activity affects the production of inflammatory cells that respond abnormally to external stimuli. This altered response causes the cells to produce modified inflammatory cytokines, showing a distinct capacity to modulate tumor growth in laboratory models.

This proof of concept demonstrates that it is possible to regulate the activity of key immune system genes such as IL1RN through DNA methylation, thereby modulating functions like inflammation or tumor progression. Although researchers already suspected that such chemical modifications could influence immune system behavior, this study provides the first experimental evidence confirming that connection and revealing its functional consequences.

With this knowledge and the technological capability to activate or deactivate individual genes with precision, the door is opened to the development of new strategies aimed at intervening in the most fundamental biological processes of immune cells and, potentially, new therapies for certain subtypes of leukemia and other diseases with an inflammatory component.

More information: Gemma Valcárcel et al, Modulating immune cell fate and inflammation through CRISPR-mediated DNA methylation editing, Science Advances (2025). DOI: 10.1126/sciadv.adt1644  Journal information: Science Advances