Alpha tocopherol ameliorates allergic airway inflammation by regulating ilc2 ferroptosis in an lkb1-dependent manner_Aa-cko VS Aa-flox
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE294318 | GEO | 2025/12/30
REPOSITORIES: GEO
Similar Datasets
Project description:Dietary immunization is vital in regulating allergic airway inflammation mediated by group 2 innate lymphoid cells (ilc2s).
2025-12-30 | GSE294316 | GEO
Project description:Our study represents LKB1 defects lead to the loss and dysfunction of adipose tissue ILC2s.And we found that LKB1 regulate ILC2s homeostasis and cytokines function in a cell-intrinsic manner.In high-diet-fed mice,LKB1 in ILC2s protects against metabolic disturbances and fat fibrosis.LKB1 deficient in ILC2 impaired the oxidative phosphorylation and led to mitochondria loss though more mitophagy.
2025-09-17 | GSE196196 | GEO
Project description:Our study represents LKB1 defects lead to the loss and dysfunction of adipose tissue ILC2s.And we found that LKB1 regulate ILC2s homeostasis and cytokines function in a cell-intrinsic manner.In high-diet-fed mice,LKB1 in ILC2s protects against metabolic disturbances and fat fibrosis.LKB1 deficient in ILC2 impaired the oxidative phosphorylation and led to mitochondria loss though more mitophagy.
2025-09-17 | GSE225097 | GEO
Project description:Group 2 innate lymphoid cells (ILC2s) mediate type 2 immune responses involved in anti-helminth immunity, allergic inflammation, and metabolic homeostasis. Recently, they have emerged as key players in regulating tumor immunity. The tumor suppressor liver kinase B1 (LKB1) inactivating mutations is associated with a variety of human cancers, but the role of LKB1 in ILC2 function and ILC2-mediated tumor immunity remains unknown. Here, we show that LKB1 is required for mature ILC2 survival. Ablation of LKB1 in ILC2s results in impaired proliferation and a marked decrease in type 2 cytokine production upon activation, accompanied with the expression of exhaustion signature genes and reduced cellular metabolism, which promote the development of lung melanoma metastasis. In addition, LKB1 deficiency leads to a marked increase of programmed cell death protein-1 (PD-1) expression in ILC2s through activation of nuclear factor of activated T cells (NFAT) pathway. Blockade of PD-1 can restore type 2 cytokine production in LKB1-deficient ILC2 and reverse its exhaustion state, leading to enhanced antitumor immune responses in vivo. Together, our results reveal that LKB1 retrains ILC2 exhaustion state to maintain immune homeostasis and their antitumor immunity.
2024-05-21 | GSE209588 | GEO
Project description:The maternal microbiota plays an important role in shaping and priming infant immunity, although the cellular and molecular mechanisms underlying these effects remain obscure. Here we report that prenatal antibiotic exposure caused significant elevation of group 2 innate lymphoid cells (ILC2s) in neonatal lungs, in both cell numbers and functionality. Downregulation of type 1 interferon signaling in ILC2s caused by diminished production of microbiota-derived metabolite butyrate represents the underlying mechanism. Mice lacking butyrate receptor GPR41 (GPR41-/-) or type 1 interferon receptor (Ifnar1-/-) recapitulated the phenotype of neonatal ILC2s upon maternal antibiotic exposure. Furthermore, prenatal antibiotic exposure induced persistent epigenetic changes in ILC2s and had a long-lasting deteriorative effect on allergic airway inflammation in adulthood. Prenatal supplementation with butyrate ameliorated airway inflammation in adult offspring born to antibiotic-exposed dams. These observations demonstrate an essential role for the maternal microbiota in the control of type 2 innate immunity at the neonatal stage, which provides a therapeutic window for treating asthma in early life.
2023-05-08 | GSE231887 | GEO
Project description:Group 2 innate lymphoid cells (ILC2s) play critical roles in allergic lung inflammation through initiating and amplifying type 2 immune responses. However, the molecular mechanisms underlying pathogenic ILC2 activation remain largely unknown. Here, we show that lung ILC2s exhibit increased mTORC1 activation in allergic asthma. Genetic ablation of RAPTOR, an adaptor protein of the mTORC1 complex, results in reduced IL-5 and IL-13 production in ILC2s and protects mice from allergic inflammation. Pharmacological inhibition of mTORC1 by rapamycin also suppresses ILC2 pathogenic activation and ameliorates allergic lung inflammation. Mechanistically, mTORC1 signaling promotes ILC2 activation through metabolic regulation of epigenetics to maintain neurointerin U receptor 1 (NMUR1) expression, which mediates neural-ILC2 interaction via the NMU-NMUR1 axis. These findings identify mTORC1 as a novel regulator to control the neural-ILC2 interaction and highlight mTORC1 as a potential therapeutic target for allergic asthma.
2025-10-30 | GSE272521 | GEO
Project description:Innate type-2 lymphocytes (ILC2s) are a newly described cell type whose biology and contribution to disease are poorly understood. We are interested in investigating the role of the transcription factor Gfi1 in ILC2s, which appear to be a prominent source of IL-5 and IL-13 during type-2 immune responses. We have compelling evidence demonstrating a critical role for Gfi1 in the development and effector state of ILC2s. We would like to elucidate the molecular role of Gfi1 in ILC2s by identifying Gfi1-regulated genes by microarray analysis. Gfi1+/+ or Gfi1GFP/GFP (a GFP cassette has been 'knocked-in' to the Gfi1 locus and thus functions both as a surrogate for Gfi1 promoter activity and as a loss-of-function allele) mice were injected with IL-25 once daily for 4 days. On day 5, ILC2s (Lin-/Sca-1+/ICOS+/CD127+/c-Kit+) were sorted from the mesenteric lymph nodes of Gfi1+/+ (3 mice/sample were pooled together) or Gfi1-/- mice (6 mice/sample were pooled together) and cultured for 6 days in RPMI 1640, 10% FBS, Gln, P/S, 2ME, IL-2 (50ng/ml), IL-7 (10ng/ml), and IL-25 (50ng/ml). Whole RNA was harvested on day 6 via the RNeasy kit (Qiagen).
2013-10-20 | E-GEOD-45621 | biostudies-arrayexpress
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
Project description:Group 2 innate lymphoid cells (ILC2s) play critical roles in allergic lung inflammation through initiating and amplifying type 2 immune responses. However, the molecular mechanisms underlying pathogenic ILC2 activation remain largely unknown. Here, we show that lung ILC2s exhibit increased mTORC1 activation in allergic asthma. Genetic ablation of RAPTOR, an adaptor protein of the mTORC1 complex, results in reduced IL-5 and IL-13 production in ILC2s and protects mice from allergic inflammation. Pharmacological inhibition of mTORC1 by rapamycin also suppresses ILC2 pathogenic activation and ameliorates allergic lung inflammation. Mechanistically, mTORC1 signaling promotes ILC2 activation through metabolic regulation of epigenetics to maintain neurointerin U receptor 1 (NMUR1) expression, which mediates neural-ILC2 interaction via the NMU-NMUR1 axis. These findings identify mTORC1 as a novel regulator to control the neural-ILC2 interaction and highlight mTORC1 as a potential therapeutic target for allergic asthma.
2025-10-30 | GSE272716 | GEO
Project description:Group 2 innate lymphoid cells (ILC2s) play critical roles in driving the pathogenesis of allergic airway inflammation. The mechanisms underlying the regulation of ILC2s remain to be fully understood. Here, we identified neuropilin-1 (Nrp1) as a surface marker of ILC2s in response to IL-33 stimulation. Nrp1 was abundantly expressed in ILC2s from lung under steady state, which was significantly reduced upon IL-33 stimulation. ILC2s with high expression of Nrp1 (Nrp1high) displayed lower response to IL-33, as compared with Nrp1low ILC2s. Transcriptional profiling and flow cytometric analysis showed that downregulation of AKT-mTOR signaling participated in the diminished functionality of Nrp1high ILC2s. These observations revealed a potential role of Nrp1 in ILC2s responses under allergic inflammatory condition.
2023-09-30 | GSE243540 | GEO