Epigenomic Views of Innate Lymphoid Cells

Abstract

The discovery of innate lymphoid cells (ILCs) with selective production of cytokines typically attributed to subsets of T helper cells forces immunologists to reassess the mechanisms by which selective effector functions arise. The parallelism between ILCs and T cells extends beyond these two cell types and comprises other innate-like T lymphocytes. Beyond the recognition of specialized effector functionalities in diverse lymphocytes, features typical of T cells, such as plasticity and memory, are also relevant for innate lymphocytes. Herein, we review what we have learned in terms of the molecular mechanisms underlying these shared functions, focusing on insights provided by next generation sequencing technologies. We review data on the role of lineage-defining- and signal-dependent transcription factors (TFs). ILC regulomes emerge developmentally whereas the much of the open chromatin regions of T cells are generated acutely, in an activation-dependent manner. And yet, these regions of open chromatin in T cells and ILCs have remarkable overlaps, suggesting that though accessibility is acquired by distinct modes, the end result is that convergent signaling pathways may be involved. Although much is left to be learned, substantial progress has been made in understanding how TFs and epigenomic status contribute to ILC biology in terms of differentiation, specification, and plasticity.

NCR+ ILC3 maintain larger STAT4 reservoir via T‐BET to regulate type 1 features upon IL‐23 stimulation in mice

“…Despite their phenotypic similarity with NK cells, NCR + ILC3 were initially identified for their ability to produce IL‐22, both in human and mouse, and lack of the typical NK cell effector functions . However, the requirement of the LDTFs of ILC1, T‐BET (encoded by Tbx21 ), functionally positions these cells as a bridge between type 1 and type 3 ILCs , and delineates their hybrid transcriptional and epigenetic programs .…”

aFARP-ChIP-seq, a convenient and reliable method for genome profiling in as few as 100 cells with a capability for multiplexing ChIP-seq

“…(f) A summary for chromatin fragmentation of 1 × 10 5 fixed mESCs by MNase and Atlantis dsDNase. The definition of digestion efficiency and over-digestion are the same as described in Figure 1 microenvironment on chromatin and gene regulatory landscapes, however, is poorly understood [12,21,26], in part, due to the difficulty in mapping chromatin and gene regulatory landscapes in ILCs isolated from individual animals. We focused our study on the IFN-γ-producing group 1 ILCs, including conventional NK and ILC1, isolated from individual mice [27].…”

“…Similar to previous epigenetic studies of developmental cell lineages, an epigenetic profile for different ILCs would help to further refine these subsets. However, the lack of high quality epigenome and chromatin protein binding profiles, due to the difficulty performing ChIP-seq on low abundance siIEL ILC1 has limited additional in-depth study of the lineage identity and origin of these cells [21].…”

aFARP-ChIP-seq, a convenient and reliable method for genome profiling in as few as 100 cells with a capability for multiplexing ChIP-seq

“…Recent studies indicate that tissue-specific signals have significant impacts on gene expression and activity of ILCs. The influence of local tissue microenvironments on chromatin and gene regulatory landscapes, however, has remained not well understood (Gury-BenAri et al, 2016a;Shih et al, 2016;Sciumè et al, 2017), in part, due to the difficulty in mapping chromatin and gene regulatory landscapes in ILCs isolated from individual animals. We focused our study on the IFN-γ-producing group 1 ILCs, including conventional NK and ILC1, isolated from individual mice Since there is a lack of unique and consistent markers in NK cells and ILC1 cells in various organs, we used different sorting strategies according to previously published protocols for each tissue, including spleen, mesenteric lymph nodes (mLN), liver and small intestine intraepithelia ( Figure 3A and Figure S2A) (Robinette et al, 2015).…”