Characterization of innate lymphoid cells under homeostatic and inflammatory conditions by epigenetic profiling

• Applicants: Dr. Stefan Flöß; Professor Dr. Matthias Lochner
• Subject Area: Immunology
• Term: from 2016 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 320269619

Epigenetic modifications such as histone acetylation or DNA methylation play an essential role for imprinting specific transcriptional pattern in cells. Here, we show that similar to CD4+ T helper lineages the gene loci of transcription factors and cytokines in innate lymphoid cells (ILC) contain differentially methylated regions (DMR), which might be critical for development and function of ILC. Genome-wide DNA methylation profiling of murine lymph node-derived ILC was established, which was used for the identification of DMR and subsequent definition of epigenetic marker regions in ILC lineages. Our epigenetic analysis also revealed a closer relationship between ILC1 and NK cells, as well as between ILC3 and LTi, whereas ILC2 appear to be more distinct. Combination of methylome and transcriptome data detected strong correlations between the methylation status of marker regions and the expression level of the associated genes, indicating their relevance for ILC biology. Importantly, initial data suggest that the epigenome of ILC is critically shaped by inflammatory reactions. In the next funding period, we will therefore study further the influence of inflammation on the defined epigenetic ILC marker in the context of local inflammation and neonatal infections. In addition, we will also determine the long-lasting effect of inflammation on DNA methylation and search for specific epigenetic marker associated with ILC memory formation. Studies on the molecular mechanisms involved in marker gene regulation will enable us to identify pathways relevant for development, specialization and activation of ILC. Finally, defining epigenetic marker regions for human ILC will move the project towards clinical use and might contribute to improved disease monitoring and therapy.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1937: Innate Lymphoid Cells