DNA methylation dynamics in the functional regulation of human T lymphocytes
Research area: Molecular Immunology
Group leaders: Silvia Monticelli
- Cristina Leoni, Scientist
Status: In progress
Efficient immune responses orchestrated by CD4+ T lymphocytes require both lineage commitment and phenotypic flexibility, allowing the development of responses tailored to invading pathogens. With this project we aim at comprehensively investigating the role of DNA modifications and DNA-modifying enzymes in human T cell responses. Specifically, we want to address fundamental questions about the gene regulatory networks controlling the balance between commitment, phenotypic stability and plasticity of T cells. This will be performed by combining genome-wide analyses of DNA modifications and genetic manipulation of primary human T cells. Indeed, the stability of DNA methylation and its heritability across mitosis make it particularly apt to mediate the maintenance of transcriptional networks and cellular phenotypes. In the case of T cells, however, stability in the expression of subset-selective genes (notably cytokine genes) must be reconciled with mechanisms enabling plastic phenotypic changes in response to environmental clues. The recent discovery that methylated DNA can be dynamically modified, impacting gene expression directly or via erasure of DNA methylation, suggests its possible role in T cell plasticity. Our study will thoroughly describe dynamics in the methylation landscape in primary human T cells in response to specific pathogens and antigens, and assess the effects of methylation dynamics in T cell functions, leading to novel insights in immunity against pathogens and in disease.