Profiling of epigenetic marker regions in murine ILCs under homeostatic and inflammatory conditions

Abstract

Epigenetic modifications such as DNA methylation play an essential role in imprinting specific transcriptional patterns in cells. We performed genome-wide DNA methylation profiling of murine lymph node–derived ILCs, which led to the identification of differentially methylated regions (DMRs) and the definition of epigenetic marker regions in ILCs. Marker regions were located in genes with a described function for ILCs, such as Tbx21, Gata3, or Il23r, but also in genes that have not been related to ILC biology. Methylation levels of the marker regions and expression of the associated genes were strongly correlated, indicating their functional relevance. Comparison with T helper cell methylomes revealed clear lineage differences, despite partial similarities in the methylation of specific ILC marker regions. IL-33–mediated challenge affected methylation of ILC2 epigenetic marker regions in the liver, while remaining relatively stable in the lung. In our study, we identified a set of epigenetic markers that can serve as a tool to study phenotypic and functional properties of ILCs.

cfDNA Methylation Profiles and T-Cell Differentiation in Women with Endometrial Polyps

“…The sequencing reads were filtered to exclude the low-quality reads (Phred score < 5), and then were aligned to the human reference genome (hg19) using BSMAP (Version 2.74) [ 18 ]. We identified the differentially methylated CpGs (DMCs) using metilene (Version 0.2-6) [ 19 ], selected the CpGs that were covered by more than 10× sequence reads, and reached the thresholds of differential methylation β ≥ 15% between the patients and controls for gene annotation. We then selected genes with more than one DMC and at least one DMC with a methylation difference > 0.5 for further analyses.…”

Interleukin 23 receptor: Expression and regulation in immune cells

“…IL-23 signaling can also expand a MAIT-17/1 phenotype [66]. These distinct subsets cannot be identified in humans, where IL23R constitutes a "core" gene for all MAIT cells [69][70][71]. The expression of IL23R is higher in human tissue-resident (mucosal, lung, skin, liver and entheses) MAIT cells [10,66], [72][73][74].…”

“…ILCs can be assigned to different subsets (ILC1, ILC2, and ILC3) that mirror the Th1, Th2, and Th17 subsets of conventional T cells. The IL-23R is mainly expressed in the ILC3 subset, both in mice [69,70] and in humans [93,94], although IL-23 enhanced the differentiation and growth of both human ILC1 and ILC3 [95].…”

Differential regulation of lineage-determining transcription factor expression in innate lymphoid cell and adaptive T helper cell subsets

“…Interestingly, most of the circulating NK cells do not express IL-7 receptor (IL-7R) but express inhibitory receptors, activating receptors and costimulatory receptors, which allow them to have certain levels of antigen-specific response in some conditions ( 18 , 19 ). Genome-wide analyses of methylation and chromatin accessibility clearly show different epigenetic modification patterns between Th cell and ILC subsets ( 20 – 25 ). Although some cytokines that are involved in the induction of LDTF expression during Th cell differentiation can also upregulate LDTF expression in mature ILCs during their activation, these signals are usually dispensable for LDTF induction during ILC development ( 21 , 26 – 28 ).…”

“…Epigenetic modifications are highly correlated with gene expression. For example, high levels of demethylation at the Tbx21 and Gata3 gene locus are detected in NK/ILC1s and ILC2s, respectively ( 20 ). Gene accessibility at the Tbx21 , Gata3 and Rorc loci in NK cells, ILC2s and ILC3s is also associated with their demethylation status ( 24 ).…”