Regulation of ILC2s by Brg1 (ATAC-seq on WT and KO ILC2eff)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE279671 | GEO | 2025/09/17
REPOSITORIES: GEO
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Project description:The alteration of chromatin status critically dictates the expansion and function of group 2 innate lymphoid cells (ILC2s), which have been shown to play a pathogenic role in allergic lung inflammation. In this study, we use multi-omics approaches to dissect the molecular mechanisms of how Brg1 regulates ILC2s in allergic lung diseases through a cell intrinsic manner. Our data indicate that Brg1 regulates ILC2 properties through orchestrating ILC2 energetic metabolism. These findings are enlightening for the understanding of ILC2-mediated pathogenesis in allergic lung inflammation and highlight Brg1 as a potential therapeutic target.
2025-09-17 | GSE279669 | GEO
Project description:The alteration of chromatin status critically dictates the expansion and function of group 2 innate lymphoid cells (ILC2s), which have been shown to play a pathogenic role in allergic lung inflammation. In this study, we use multi-omics approaches to dissect the molecular mechanisms of how Brg1 regulates ILC2s in allergic lung diseases through a cell intrinsic manner. Our data indicate that Brg1 regulates ILC2 properties through orchestrating ILC2 energetic metabolism. These findings are enlightening for the understanding of ILC2-mediated pathogenesis in allergic lung inflammation and highlight Brg1 as a potential therapeutic target.
2025-09-17 | GSE279668 | GEO
Project description:The alteration of chromatin status critically dictates the expansion and function of group 2 innate lymphoid cells (ILC2s), which have been shown to play a pathogenic role in allergic lung inflammation. In this study, we use multi-omics approaches to dissect the molecular mechanisms of how Brg1 regulates ILC2s in allergic lung diseases through a cell intrinsic manner. Our data indicate that Brg1 regulates ILC2 properties through orchestrating ILC2 energetic metabolism. These findings are enlightening for the understanding of ILC2-mediated pathogenesis in allergic lung inflammation and highlight Brg1 as a potential therapeutic target.
2025-09-17 | GSE279667 | GEO
Project description:The alteration of chromatin status critically dictates the expansion and function of group 2 innate lymphoid cells (ILC2s), which have been shown to play a pathogenic role in allergic lung inflammation. In this study, we use multi-omics approaches to dissect the molecular mechanisms of how Brg1 regulates ILC2s in allergic lung diseases through a cell intrinsic manner. Our data indicate that Brg1 regulates ILC2 properties through orchestrating ILC2 energetic metabolism. These findings are enlightening for the understanding of ILC2-mediated pathogenesis in allergic lung inflammation and highlight Brg1 as a potential therapeutic target.
2025-09-17 | GSE279672 | GEO
Project description:The alteration of chromatin status critically dictates the expansion and function of group 2 innate lymphoid cells (ILC2s), which have been shown to play a pathogenic role in allergic lung inflammation. In this study, we use multi-omics approaches to dissect the molecular mechanisms of how Brg1 regulates ILC2s in allergic lung diseases through a cell intrinsic manner. Our data indicate that Brg1 regulates ILC2 properties through orchestrating ILC2 energetic metabolism. These findings are enlightening for the understanding of ILC2-mediated pathogenesis in allergic lung inflammation and highlight Brg1 as a potential therapeutic target.
2025-09-17 | GSE279670 | GEO
Project description:The chromatin status fluctuates with effector and memory group 2 innate lymphoid cell (ILC2) responses. How this intricate coordination affects allergic lung inflammation remains unclear. Here, we report that during papain-induced lung inflammation, the expression of chromatin remodeler Brg1 is upregulated by IL-33 in ILC2s, accompanied with more open chromatin regions having increased accessibility. Brg1 expression is also upregulated in asthma patients’ ILC2s. Ablating Brg1 constrains ILC2 expansion and ameliorates both acute and alarmin-rechallenged secondary lung inflammation. Mechanistically, Brg1 imprints the chromatin landscape favoring aerobic glycolysis, the metabolic process reinforced in effector and memory ILC2s, to facilitate ILC2 expansion. Particularly, Brg1-augmented Hif1a enhancer accessibility is a sustained epigenetic signature in memory ILC2s inherited from effector ILC2s, and Hif1a enhances effector and memory ILC2 responses. Pharmacological inhibition of Brg1, rather than dexamethasone treatment, in acute phase is sufficient to alleviate secondary lung inflammation, highlighting Brg1 as a promising therapeutic target.
2025-09-17 | GSE279674 | GEO
Project description:Group 2 innate lymphoid cells (ILC2s) in the lung are stimulated by inhaled allergens. ILC2s do not directly recognize allergens but they are stimulated by cytokines including interleukin (IL)-33 released by damaged epithelium.Lung ILC2s, upon stimulation, produce T helper 2 cell-type cytokines inducing T cell independent allergic lung inflammation. We now report that lung ILC2s, upon activation by an allergen or IL-33, acquire the properties of memory cells. The activated ILC2s initially proliferate and secrete cytokines, followed by a contraction phase as they stop producing cytokines. Nevertheless, some persist long after the resolution of the inflammation and acquire intrinsic capacities to react to unrelated allergens more vigorously than naïve ILC2s, thus mediating a severe allergic lung inflammation. Gene expression profiles of the previously activated ILC2s show a gene signature of memory T cells. These antigen non-specific memory ILC2s may explain why asthma patients are often sensitized to multiple allergens. ILC2s were isolated from mouse lungs from naive and IL-33 injected mice 4 days, 14 days and 4 months after the initial treatment. RNA was extracted from those ILC2 populations and analyzed for gene expression profiles. RNA was also extracted from ILC2s isolated from lung draining mediastinal lymph node (mLN) 4 days and 14 days after IL-33 treatment.
2016-06-30 | E-GEOD-81700 | biostudies-arrayexpress
Project description:Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here we report that Piezo1 channels repress group 2 innate lymphoid cells (ILC2s)-driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we further found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment notably reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma.
2024-02-20 | GSE255882 | GEO
Project description:Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here we report that Piezo1 channels repress group 2 innate lymphoid cells (ILC2s)-driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we further found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment notably reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma.
2024-02-20 | GSE255881 | GEO
Project description:E-protein transcription factors (TFs) limit group 2 innate lymphoid cell (ILC2) development while promoting T cell differentiation from common lymphoid progenitors (CLPs). Inhibitors of DNA-binding (Id) proteins block E-protein DNA binding in CLPs to allow ILC2 development. However, whether E-proteins influence ILC2 function upon maturity and activation remains unclear. Mice that overexpress Id1 under control of the thymus-restricted proximal Lck promoter (Id1tg/WT) have a large pool of primarily thymus-derived ILC2s in the periphery that develop in the absence of E-protein activity. We used these mice to investigate how the absence of E-protein activity affects ILC2 function and genomic landscape in response to house dust mite (HDM) allergens. Id1tg/WT mice had increased Klrg1- ILC2s in the lung compared to wild type (WT, Id1WT/WT) mice in response to HDM, but Id1tg/WT ILC2s had an impaired capacity to produce type 2 cytokines. Analysis of WT ILC2 accessible chromatin suggested that AP-1 and C/EBP TFs but not E-proteins were associated with ILC2 inflammatory gene programs. Instead, E-protein binding sites were enriched at functional genes in ILC2s during development that were later dynamically regulated in allergic lung inflammation, including genes that control ILC2 response to cytokines and interactions with T cells. Finally, ILC2s from Id1tg/WT compared to WT mice had fewer regions of open chromatin near functional genes that were enriched for AP-1 factor binding sites following HDM treatment. These data show that E-proteins shape the chromatin landscape during ILC2 development to dictate the functional capacity of mature ILC2s during allergic inflammation in the lung.
2021-10-18 | GSE185950 | GEO