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Distinct Gene Regulatory Pathways for Human Innate Versus Adaptive Lymphoid Cells [ChIP-seq & ATAC-seq]

ABSTRACT: Innate lymphoid cells (ILCs) serve as sentinels in mucosal tissues, sensing release of soluble inflammatory mediators, rapidly communicating danger via cytokine secretion, and functioning as guardians of tissue homeostasis. Although ILCs have been studied extensively in model organisms, little is known about these “first responders” in humans, especially their lineage and functional kinships to cytokine-secreting T helper cell (Th) counterparts. Here, we report gene regulatory circuitries for four human ILC–Th counterparts derived from mucosal environments, revealing that each ILC subset diverges as a distinct lineage from Th and circulating natural killer cells, but shares circuitry devoted to functional polarization with their Th counterparts. Super-enhancers demarcate cohorts of cell identity genes in each lineage, uncovering new modes of regulation for signature cytokines, novel molecules that likely impart important functions to ILCs, and potential mechanisms for autoimmune disease SNP associations within ILC–Th subsets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE77299 | GEO | 2016/05/13

SECONDARY ACCESSION(S): PRJNA309990

REPOSITORIES: GEO

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Distinct Gene Regulatory Pathways for Human Innate Versus Adaptive Lymphoid Cells [gene expression]

Project description:Innate lymphoid cells (ILCs) serve as sentinels in mucosal tissues, sensing release of soluble inflammatory mediators, rapidly communicating danger via cytokine secretion, and functioning as guardians of tissue homeostasis. Although ILCs have been studied extensively in model organisms, little is known about these âfirst respondersâ in humans, especially their lineage and functional kinships to cytokine-secreting T helper cell (Th) counterparts. Here, we report gene regulatory circuitries for four human ILCâTh counterparts derived from mucosal environments, revealing that each ILC subset diverges as a distinct lineage from Th and circulating natural killer cells, but shares circuitry devoted to functional polarization with their Th counterparts. Super-enhancers demarcate cohorts of cell identity genes in each lineage, uncovering new modes of regulation for signature cytokines, novel molecules that likely impart important functions to ILCs, and potential mechanisms for autoimmune disease SNP associations within ILCâTh subsets. RNA was isolated from two to five replicates of ILC1, ILC3, Th1, Th2 and NK cells. Gene expression levels were determined using Affymetrix Human Gene 1.0 ST arrays.

2016-05-13 | E-GEOD-78896 | biostudies-arrayexpress

Distinct Gene Regulatory Pathways for Human Innate Versus Adaptive Lymphoid Cells [ChIP-seq & ATAC-seq]

Project description:Innate lymphoid cells (ILCs) serve as sentinels in mucosal tissues, sensing release of soluble inflammatory mediators, rapidly communicating danger via cytokine secretion, and functioning as guardians of tissue homeostasis. Although ILCs have been studied extensively in model organisms, little is known about these âfirst respondersâ in humans, especially their lineage and functional kinships to cytokine-secreting T helper cell (Th) counterparts. Here, we report gene regulatory circuitries for four human ILCâTh counterparts derived from mucosal environments, revealing that each ILC subset diverges as a distinct lineage from Th and circulating natural killer cells, but shares circuitry devoted to functional polarization with their Th counterparts. Super-enhancers demarcate cohorts of cell identity genes in each lineage, uncovering new modes of regulation for signature cytokines, novel molecules that likely impart important functions to ILCs, and potential mechanisms for autoimmune disease SNP associations within ILCâTh subsets. Molecular profiling of innate lymphoid and T helper cells subsets purified from tonsils and NK cells purified from peripheral blood using Assay for Transposase-Accessible Chromatin (ATAC) and chromatin immunoprecipitation (H3K4me3 and H3K27ac).

2016-05-13 | E-GEOD-77299 | biostudies-arrayexpress

Distinct Gene Regulatory Pathways for Human Innate Versus Adaptive Lymphoid Cells [gene expression]

Project description:Innate lymphoid cells (ILCs) serve as sentinels in mucosal tissues, sensing release of soluble inflammatory mediators, rapidly communicating danger via cytokine secretion, and functioning as guardians of tissue homeostasis. Although ILCs have been studied extensively in model organisms, little is known about these “first responders” in humans, especially their lineage and functional kinships to cytokine-secreting T helper cell (Th) counterparts. Here, we report gene regulatory circuitries for four human ILC–Th counterparts derived from mucosal environments, revealing that each ILC subset diverges as a distinct lineage from Th and circulating natural killer cells, but shares circuitry devoted to functional polarization with their Th counterparts. Super-enhancers demarcate cohorts of cell identity genes in each lineage, uncovering new modes of regulation for signature cytokines, novel molecules that likely impart important functions to ILCs, and potential mechanisms for autoimmune disease SNP associations within ILC–Th subsets.

2016-05-13 | GSE78896 | GEO

Transcriptional profiles of human circulating innate lymphoid cells and CD4 T helper cells

Project description:Innate lymphoid cells (ILCs) are part of the innate immune cell family. Three different subsets of ILCs, ILC1s, ILC2s and ILCPs can be identified in human peripheral blood. Based on their expression of transcription factors and cytokines, they are considered as being the innate counterparts of CD4 T helper subsets, namely Th1s, Th2s and Th17s. However, ILCs and Th cells have different roles in immunity. Therefore, we compared the transcriptomes of sorted ILC1s, ILC2s, ILCPs, Th1s, Th2s and Th17s from the peripheral blood of three different donors. RNA sequencing of ILC and Th subsets revealed differences in the expression of tens to hundreds of genes. These genes are involved in cell trafficking, innate activation and inhibitory functions. ILC and Th cell subsets also differ in their expressions of long-non coding RNAs.

2020-02-04 | E-MTAB-8494 | biostudies-arrayexpress

CD45RA+CD62L- ILCs represent a quiescent local reservoir for the generation of mature ILC in human tissues

Project description:Innate lymphoid cells (ILCs) are highly plastic and predominantly mucosal tissue-resident cells that contribute to both homeostasis and inflammation depending on the microenvironment. The recent discovery of naïve-like tissue-resident ILCs suggests an ILC differentiation process that is akin to naïve T cell differentiation. Delineating the naïve-like ILC heterogeneity and the transcriptional, epigenetic and functional mechanisms that underlie ILC differentiation in tissues is crucial for understanding ILC biology in health and disease. Here we show that CD62L distinguishes two subsets of naïve-like CD45RA+ ILCs in tonsil tissue. While both subsets contain uni- and multipotent precursors of ILC1/NK cells and ILC3, CD62L+ ILCs resemble bona fide naïve ILCs with metabolism reminiscent of naïve T cells, lacking transcriptional and epigenetic signatures of mature ILCs. CD62L- ILCs are epigenetically similar to, but transcriptionally distinct from CD62L+ naïve-like ILCs including transcripts of cytokine signaling and metabolic pathways related to mature ILCs. A similar population of CD62L- quiescent ILCs with preferential differentiation capacity towards IL-22-producing ILC3 accumulate in the inflamed mucosa of patients with inflammatory bowel disease (IBD). These data suggest that naïve-like and quiescent ILCs are imprinted by their tissue microenvironment that poises their differentiation potential. Our findings identify restoration of homeostatic IL-22-producing ILC3 from CD62L- quiescent ILCs as a potential approach to improve tissue healing in IBD.

2022-02-17 | GSE176367 | GEO

The spectrum and regulatory landscapes of intestinal innate lymphoid cells are shaped by the microbiome (ATAC-Seq)

Project description:Innate lymphoid cells (ILCs) are critical modulators of mucosal immunity, inflammation, and tissue homeostasis, but their full spectrum of cellular states and regulatory landscapes remain elusive. Here, we use a combination of genome-wide RNA-seq, ChIP-seq and ATAC-seq to compare the transcriptional and epigenetic identity of small intestinal ILCs, identifying thousands of distinct gene profiles and regulatory elements. Single-cell RNA-seq, cytometry, and imaging analyses reveal functional compartmentalization of cytokine expression and metabolic activity within the three classical ILC subtypes, and highlight transcriptional states beyond the current canonical classification. In addition, using antibiotic intervention and germ-free mice, we characterize the effect of the microbiome on the ILC regulatory landscape, and determine the response of ILCs to microbial colonization at the single-cell level. Together, our work characterizes the spectrum of transcriptional identities of small intestinal ILCs and describes how ILCs differentially integrate signals from the microbial microenvironment to generate phenotypic and functional plasticity.

2016-08-18 | GSE85153 | GEO

The spectrum and regulatory landscapes of intestinal innate lymphoid cells are shaped by the microbiome (single cells)

2016-08-18 | GSE85152 | GEO

The spectrum and regulatory landscapes of intestinal innate lymphoid cells are shaped by the microbiome (ChIP-Seq)

2016-08-18 | GSE85156 | GEO

The spectrum and regulatory landscapes of intestinal innate lymphoid cells are shaped by the microbiome (RNA-Seq)

2016-08-18 | GSE85154 | GEO

Characterization of rat ILCs reveals ILC2 as the dominant intestinal subset

Project description:Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that lack antigen-specific receptors and exhibit innate effector functions such as cytokine production that play an important role in immediate responses to pathogens especially at mucosal sites. Mouse and human ILC subsets have been extensively characterized in various tissues and in blood. In this study, we present the first characterization of ILCs and ILC subsets in rat gut and secondary lymphoid organs. ScRNAseq and flow cytometric data shows that phenotype and function of rat ILC subsets are conserved similar to human and mouse ILCs. However, contrary to human and mouse, our study unexpectedly revealed that ILC2 and not ILC3 was by far the dominant ILC subset in the rat intestinal lamina propria. ILC2 predominance in the gut was independent of rat strain, sex or housing facility. In contrast, ILC3 were the main ILC subset in mesenteric lymph nodes and Peyer patches, in which strain-dependent differences in ILC frequencies were also observed. In conclusion, our study demonstrates that in spite of highly conserved phenotype and function between mice, rat and humans, the distribution of ILC subsets in the intestinal mucosa is species-dependent, likely in response to both genetic and environmental factors.

2020-02-12 | GSE143920 | GEO

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