Researchers at the Josep Carreras Institute have used CRISPR-based epigenetic editing to precisely control IL1RN gene expression in leukemia-derived immune cells. The study, published in Science Advances, provides experimental evidence that altering DNA methylation status can modulate inflammatory responses and influence tumor growth.
Led by Gemma Valcárcel, in collaboration with Esteban Ballestar’s group, the team used a dCas9 system to add or remove methyl groups at the IL1RN promoter. This method allowed them to switch the gene on or off in a targeted and reversible manner, without altering the underlying DNA sequence. The approach enabled direct investigation of how DNA methylation affects gene regulation in immune cells.
Controlling IL1RN expression affected how leukemia-derived cells responded to external stimuli. Cells with the gene silenced or activated produced different inflammatory cytokine profiles, which showed distinct effects on tumor growth in preclinical models.
The study offers proof that IL1RN gene activity can be modulated through DNA methylation, linking epigenetic control to immune cell behavior. Although methylation has long been suspected to influence immune pathways, this work provides one of the first demonstrations of its functional impact using targeted editing in human cells. These findings support further exploration of methylation-based interventions to study or potentially manage inflammation in leukemia and other diseases with immune dysregulation.
Publication Details
Gemma Valcárcel et al., Modulating immune cell fate and inflammation through CRISPR-mediated DNA methylation editing. Science Advances. 11, eadt1644 (2025). DOI:10.1126/sciadv.adt1644
Led by Gemma Valcárcel, in collaboration with Esteban Ballestar’s group, the team used a dCas9 system to add or remove methyl groups at the IL1RN promoter. This method allowed them to switch the gene on or off in a targeted and reversible manner, without altering the underlying DNA sequence. The approach enabled direct investigation of how DNA methylation affects gene regulation in immune cells.
Controlling IL1RN expression affected how leukemia-derived cells responded to external stimuli. Cells with the gene silenced or activated produced different inflammatory cytokine profiles, which showed distinct effects on tumor growth in preclinical models.
The study offers proof that IL1RN gene activity can be modulated through DNA methylation, linking epigenetic control to immune cell behavior. Although methylation has long been suspected to influence immune pathways, this work provides one of the first demonstrations of its functional impact using targeted editing in human cells. These findings support further exploration of methylation-based interventions to study or potentially manage inflammation in leukemia and other diseases with immune dysregulation.
Publication Details
Gemma Valcárcel et al., Modulating immune cell fate and inflammation through CRISPR-mediated DNA methylation editing. Science Advances. 11, eadt1644 (2025). DOI:10.1126/sciadv.adt1644