PD-1 regulates ILC3-driven intestinal immunity and homeostasis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1074317 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:PD-1 regulates ILC3-driven intestinal immunity and homeostasis
| PRJNA1071708 | ENA
Project description:PD-1 is constitutively expressed on a fraction of ILC3 in the gut. To identify the transcriptional differences between PD1+ and PD1- ILC3, we have sorted these subsets and analysed their transcriptional regulation by RNA-Seq.
2024-02-29 | GSE254794 | GEO
Project description:Interleukin-(IL) 22 production by intestinal group 3 innate lymphoid cells (ILC3) is critical to maintain gut homeostasis. However, IL-22 needs to be tightly controlled; reduced IL-22 expression is associated with intestinal epithelial barrier defect while its overexpression promotes tumor development. Here, using a single cell RNAseq approach, we identified a core set of genes associated with increased IL-22 production by ILC3.
2025-02-28 | GSE255270 | 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
Project description:Type-3 innate lymphoid cells (ILC3) regulate homeostasis and orchestrate immunity in the intestine, mediated in part by their bi-directional communication with the intestinal epithelium. In order to define specific interactions between these two compartments, we used a reductionist co-culture system of murine epithelial small intestinal organoids (SIO) with ILC3. The transcriptomic profile of epithelial cells from these co-cultures was analysed by bulk RNAseq.
2023-12-07 | GSE243737 | GEO
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:Regulatory T cells (Tregs) have an immunosuppressive function and highly express PD-1 in tumor microenvironment, but the function of PD-1 in Tregs is still controversial. Using murine tumor model, we demonstrated that Tregs-specific PD-1 conditional Knock-Out mice are resistant to tumor progression. Using PD-1 hetero conditional Knock-Out mice in which both PD-1 expressing Tregs and deficient Tregs co-exist, we found that specific ablation of PD-1 on Tregs results in impaired proliferative capacity and functionality of Tumor-infiltrating Tregs. Single cell RNA and VDJ sequencing revealed that PD-1 signaling in TI Tregs induces global transcriptome crucial for Tregs homeostasis and functionality. Taken together, we suggest that specific ablation of PD-1 on Tregs promotes antitumor immunity by exacerbating Tregs stability and functionality.
2020-12-31 | GSE164033 | GEO
Project description:Innate lymphoid cells (ILCs) are able to directly respond to alarmin signals and produce an array of effector molecules for immune protection and tissue homeostasis. However, how posttranscriptional machinery in ILCs execute extracellular stimuli towards robust gene expression is yet to understand. Here, we reported a cell type-specific role of N6-methyladenosine (m6A) RNA methylation in ILCs. Inducible deletion of m6A methyltransferase METTL3 had little impact on ILC maintenance in the steady state or cytokine-induced ILC1 or ILC3 activation, but dramatically diminished IL-25-triggered ILC2 response. Specific deletion of Mettl3 in ILC2 significantly attenuated cell expansion, cytokine production, inter-organ migration, and anti-helminth immunity. To investigate the molecular mechanism by which m6A modification regulates ILC response, we subjected IL-1 plus IL-23-activated ILC3 to a m6A-tagged mRNA immunoprecipitation sequencing (meRIP-seq) to identify the m6A modified mRNA.
2023-06-26 | GSE223083 | GEO
Project description:Light-entrained and brain-tuned circadian circuits regulate ILC3 and gut homeostasis
| PRJNA558083 | ENA
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