Reciprocal Transcription Factor Networks Govern Tissue-Resident ILC3 Subset Function and Identity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA685109 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13251090.fastq.gz | Fastqsanger.gz | |||
| SRR13251091.fastq.gz | Fastqsanger.gz | |||
| SRR13251092.fastq.gz | Fastqsanger.gz | |||
| SRR13251093.fastq.gz | Fastqsanger.gz | |||
| SRR13251094.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 10 |
Similar Datasets
Project description:Innate lymphoid cells (ILCs) play important roles in health and tissue homeostasis. While the transcriptional networks that drive their development have been defined, the transcriptional requirements that support the phenotypes and functions of mature tissue-resident populations remain poorly understood. Here we employed combinatorial inducible deletion of core transcription factors (TFs) to test how co-operative and antagonistic networks operate to control function and identity. Utilizing single cell sequencing and epigenetic profiling we dissect the complex interplay between ROR family member TFs and T-bet in determining the function and phenotype of ILC3 and NCR-lineage ILCs, defining the ontogeny and surface phenotype across a continuum of ILC3s and mature ILC1s in the small intestine, alongside the differential requirements for ROR family TFs in the maintenance of effector functions and phenotype in mature ILCs. Combined, our data demonstrates how TF networks integrate in vivo to sustain effector functions and restrict alternative differentiation programmes.
2021-09-23 | GSE163149 | GEO
Project description:Innate lymphoid cells (ILCs) are guardians of mucosal immunity, yet the transcriptional networks that support their function remain poorly understood. We used inducible combinatorial deletion of key transcription factors (TFs) required for ILC development (RORγt, RORα and T-bet) to determine their necessity in maintaining ILC3 identity and function. Both RORγt and RORα were required to preserve optimum effector functions; however, RORα was sufficient to support robust interleukin-22 production among the lymphoid tissue inducer (LTi)-like ILC3 subset, but not natural cytotoxicity receptor (NCR)+ ILC3s. Lymphoid tissue inducer-like ILC3s persisted with only selective loss of phenotype and effector functions even after the loss of both TFs. In contrast, continued RORγt expression was essential to restrain transcriptional networks associated with type 1 immunity within NCR+ ILC3s, which coexpress T-bet. Full differentiation to an ILC1-like population required the additional loss of RORα. Together, these data demonstrate how TF networks integrate within mature ILCs after development to sustain effector functions, imprint phenotype and restrict alternative differentiation programs.
| S-EPMC7611981 | biostudies-literature
Project description:Innate lymphoid cells (ILC) are tissue-resident effector cells with important roles in tissue homeostasis, protective immunity and inflammatory disease. Current nomenclature divides ILC into subsets based on the expression of master transcription factors and effector cytokine programs. In mucosal barrier tissues, group 3 ILC (ILC3) have been defined by the expression of the master transcription factor RORgt. However, ILC3 can be further subdivided into two major subsets – natural cytotoxicity receptor-expressing (NCR+) ILC3 and lymphoid tissue inducer (LTi)-like ILC3 which share type 3 effector modules but also exhibit significant ontological, transcriptional, phenotypic and functional heterogeneity. In particular, LTi-like ILC3 exhibit effector functions not typically associated with other RORgt-expressing lymphocytes, provoking the hypothesis that other master transcription factors may contribute to LTi-like ILC3 biology. Here we identify Bcl6 as an LTi-like ILC3 associated transcription factor in both mice and humans. Deletion of Bcl6 led to dysregulation of the LTi-like ILC3 transcriptional program and changes to subset-specific phenotypic markers and effector functions. Strikingly, loss of Bcl6 enhanced expression of the type 3 effector cytokines IL-17A and IL-17F in LTi-like ILC3, which was found to be in part dependent upon the commensal microbiota. Together these findings implicate Bcl6 as an ILC3 subset-defining transcription factor and part of a network that confers phenotype and function on LTi-like ILC3. Our study further provides a missing link to redefine analogous immune modules in innate and adaptive lymphocyte responses.
2023-10-31 | GSE228852 | GEO
Project description:Bcl6 is a subset defining transcription factor of Lymphoid Tissue inducer-like ILC3
| PRJNA951730 | ENA
Project description:Autoimmune regulator (Aire) plays an indispensable role in the induction of central immune tolerance. We identify a novel subset of Rorγt-dependent innate lymphoid cell-type in secondary lymphoid organs, which presents endogenously generated antigens and contributes to peripheral T cell tolerance. In this experiment, transcriptomes of these Aire-ILC3 cells are characterized in wild-type Balb/C and Aire-/- Balb/C mice [Ramsey, C. et al. (2002) Hum Mol Genet 11:397-409] using RNA-seq method. To obtain the cells, peripheral lymph nodes were minced, enzymatically digested, and Aire-ILC3 cells were FACS-sorted as Lin-, MHCII+, CD80+, IL7Ra+ cells.
2019-03-14 | E-MTAB-7088 | biostudies-arrayexpress
Project description:Group 3 innate lymphoid cells (ILC3) are innate immune effectors that contribute to host defense. Whether ILC3 functions are stably modified following pathogen encounter is unknown. Here we assess the impact of a time-restricted enterobacterial challenge to long-term ILC3 activation. We found that intestinal ILC3 persist for months in an activated state following exposure to Citrobacter rodentium. Upon rechallenge, these “trained” ILC3 proliferate, display enhanced interleukin (IL)-22 responses, and have a superior cell-intrinsic capacity to control infection compared to naïve ILC3. Metabolic changes occur in C. rodentium-exposed ILC3 but only trained ILC3 have enhanced proliferative capacity that contributes to elevated IL-22 production. Accordingly, a limited encounter with a pathogen can promote durable phenotypic and functional changes in intestinal ILC3 that contribute to long-term mucosal defense.
2022-01-31 | GSE191167 | GEO
Project description:Tissue-resident innate lymphoid cells (ILCs) help sustain barrier function and respond to local signals. ILCs are traditionally classified as ILC1, ILC2 or ILC3 on the basis of their expression of specific transcription factors and cytokines1. In the skin, disease-specific production of ILC3-associated cytokines interleukin (IL)-17 and IL-22 in response to IL-23 signalling contributes to dermal inflammation in psoriasis. However, it is not known whether this response is initiated by pre-committed ILCs or by cell-state transitions. Here we show that the induction of psoriasis in mice by IL-23 or imiquimod reconfigures a spectrum of skin ILCs, which converge on a pathogenic ILC3-like state. Tissue-resident ILCs were necessary and sufficient, in the absence of circulatory ILCs, to drive pathology. Single-cell RNA-sequencing (scRNA-seq) profiles of skin ILCs along a time course of psoriatic inflammation formed a dense transcriptional continuum—even at steady state—reflecting fluid ILC states, including a naive or quiescent-like state and an ILC2 effector state. Upon disease induction, the continuum shifted rapidly to span a mixed, ILC3-like subset also expressing cytokines characteristic of ILC2s, which we inferred as arising through multiple trajectories. We confirmed the transition potential of quiescent-like and ILC2 states using in vitro experiments, single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) and in vivo fate mapping. Our results highlight the range and flexibility of skin ILC responses, suggesting that immune activities primed in healthy tissues dynamically adapt to provocations and, left unchecked, drive pathological remodelling.
2020-12-14 | GSE149622 | GEO
Project description:Small intestinal group 3 innate lymphoid cells (ILC3) from ILC3-conditional BMAL1 knock out mice or littermate control mice were sort-purified for transcriptional analysis
2019-08-28 | GSE135359 | GEO
Project description:ILC3 contain 3 well-defined subsets, CCR6+ ILC3, NKp46+ ILC3, and CCR6–NKp46– DN ILC3. These subsets had not previously been transcriptionally compared and the extent to which they had shared or unique transcriptional profiles remained unclear. We used microarray to determine transcriptional differences between these 3 subsets and to find putative factors that support the survival of CCR6+ ILC3 during cytokine depletion.
2017-02-10 | GSE92693 | GEO
Project description:Group 3 innate lymphoid cells (ILC3) are major regulators of inflammation, infection, microbiota composition and metabolism. ILC3 and neuronal cells were shown to interact at discrete mucosal locations to steer mucosal defence. Nevertheless, whether neuroimmune circuits operate at an organismal level, integrating extrinsic environmental signals to orchestrate ILC3 responses remains elusive. Here we show that light-entrained and brain-tuned circadian circuits regulate enteric ILC3, intestinal homeostasis and the host lipid metabolism. We found that enteric ILC3 display circadian expression of clock genes and ILC3-related transcription factors. ILC3-autonomous ablation of the circadian regulator Arntl led to disrupted gut ILC3 homeostasis, impaired epithelial reactivity, deregulated microbiome, increased susceptibility to bowel infection and disrupted lipid metabolism. Loss of ILC3-intrinsic Arntl shaped the gut postcode receptors of ILC3. Strikingly, light-dark cycles, feeding rhythms and microbial cues differentially regulated ILC3 clocks, with light signals as major entraining cues of ILC3. Accordingly, surgical- and genetically-induced deregulation of brain rhythmicity led to disrupted circadian ILC3 oscillations, deregulated microbiome and altered lipid metabolism. Our work reveals a circadian circuitry that translates environmental light cues into enteric ILC3, shaping intestinal health and organismal homeostasis.
2019-08-02 | GSE135235 | GEO