Ontology highlight
ABSTRACT:
PROVIDER: PRJNA433909 | ENA |
REPOSITORIES: ENA
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Project description:Runx/Cbfβ complexes protect ILC2s from exhaustion during allergic airway inflammation
| PRJNA438449 | ENA
Project description:Group 2 innate lymphoid cells (ILC2s) have tissue-resident competence and contribute to the pathogenesis of allergic diseases. Therefore, there should be mechanisms to maintain the capacity of ILC2s to produce TH2 cytokines under chronic inflammatory conditions. Here, we report that Runx proteins are essential to prevent exaggerated activation of ILC2, in part by antagonizing GATA-3 function at steady state. However, during allergic inflammation, the absence of Runx in ILC2s impaired their ability to proliferate and produce effector TH2 cytokines and chemokines, but instead induced expression of T cell exhaustion markers including IL-10 and TIGIT. These exhausted ILC2s were unabale to induce type 2 immune responses against repeated allergen inhalation. Thus, Runx proteins protect ILC2s from exhaustion during continuous allergic inflammation.
2019-01-07 | GSE111871 | GEO
Project description:Group-2 innate lymphoid cells (ILC2) are tissue-resident, long-lived innate effector cells implicated in allergy and asthma. Upon activation, mature ILC2 rapidly secret large amounts of type-2 cytokines and other effector molecules. The molecular pathways that drive ILC2 activation are not well understood. Here we report that the transcriptional controller Core-binding factor β (CBFβ) is required for ILC2 activation. Deletion or inhibition of CBFβ did not impair the maintenance of ILC2 at homeostasis, but abolished ILC2 activation during allergic airway inflammation. Treatment with CBFβ inhibitors prevented ILC2-mediated airway hyperresponsiveness in a mouse model of acute Alternaria allergen inhalation. CBFβ promoted expression of key ILC2 genes at both transcriptional and translational levels. CBF transcriptional complex directly bound to Il13 and Vegfa promoters and enhancers, and controlled gene transcription. CBFβ further promoted ribosome biogenesis and enhanced gene translation in activated ILC2. Together, these data establish an essential role for CBFβ in ILC2 activation.
2019-01-23 | GSE116062 | GEO
Project description:Group 2 innate lymphoid cells (ILC2s) play a crucial role in allergic diseases by coordinating a complex network of various effector cell lineages involved in type 2 inflammation. However, their function in regulating airway neutrophil infiltration, a deleterious symptom of severe asthma, remains unknown. Here, we observed ILC2-dependent neutrophil accumulation in the bronchoalveolar lavage fluid (BALF) of allergic mice models. Chromatography followed by proteomics analysis identified the alarmin high mobility group box-1 (HMGB1) in the supernatant of lung ILC2s initiated neutrophil chemotaxis. Genetic perturbation of Hmgb1 in ILC2s reduced BALF neutrophil numbers and alleviated airway inflammation. HMGB1 was loaded onto the membrane of lipid droplets (LDs) released from activated lung ILC2s. Genetic inhibition of LD accumulation in ILC2s significantly decreased extracellular HMGB1 abundance and BALF neutrophil infiltration. These findings unveil a previously uncharacterized extracellular LD-mediated immune signaling delivery pathway by which ILC2s regulate airway neutrophil infiltration during allergic inflammation.
2024-09-21 | GSE245964 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE35979: Gene expression data from IL13-induced allergic airway inflammation of mice lungs GSE35980: MicroRNA expression data from IL13-induced allergic airway inflammation of mice lungs GSE37079: Methylated DNA immunoprecipitation (MeDIP) microarray data from IL13-induced allergic airway inflammation of mouse lungs Refer to individual Series
2012-04-06 | E-GEOD-37085 | biostudies-arrayexpress
Project description:Group-2 innate lymphoid cells (ILC2) serve crucial function in allergy and asthma. Activated ILC2 rapidly proliferate and secret large amounts of type-2 cytokines, such as IL-5 and IL-13. Mechanisms underlying still remain ambiguous. Here we report that Myc is required for ILC2 proliferation and activation in allergic airway inflammation. Inhibition of Myc impair the ILC2 proliferation in vivo and prevented ILC2-mediated airway hyperresponsiveness in vivo. We used microarrays to detail the global programme of different gene expression between WT and Myc KO in ILC2.
2020-01-01 | GSE129309 | GEO
Project description:Obesity is associated with severe, difficult to control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment strategy. Using a mouse model of house dust mite (HDM) induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ); we investigated the effects of obesity and mROS on airway inflammation, remodelling and airway hyperreactivity (AHR). HDM induces airway inflammation, remodelling and hyperreactivity in both lean and obese mice. Obese allergic mice showed increased lung tissue eotaxin levels, airway tissue eosinophilia and AHR when compared to lean allergic mice. MitoQ reduced markers of airway inflammation, remodelling and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obeseHDM mice. mROS regulates cell signalling by protein oxidation of multiple downstream targets: MitoQ reduced HDM-induced cysteine-sulfenylation of several proteins including those involved in the unfolded protein response (UPR). In summary, mROS mediates the development of allergic airway disease and hence MitoQ might be effective for the treatment for asthma, and specific features of obese asthma.
2023-06-02 | PXD029715 | Pride
Project description:Allergic asthma is a leading chronic disease associated with airway hyperreactivity (AHR). Type-2 innate lymphoid cells (ILC2s) are a potent source of T-helper 2 cytokines that promote AHR and lung inflammation. In this study, we evaluated the protective role of PD-1 on the development of AHR by focusing on its capacity to regulate ILC2 activation. We find that PD-1 is highly inducible in pulmonary ILC2s and shapes their transcriptional activity, activation and metabolism. Our findings provide new insights regarding the mechanisms of ILC2 regulation, which could be used in innovative approaches for the treatment of allergic asthma.
2020-07-08 | GSE153909 | GEO
Project description:Fungal spores, abundant in the environment, are a major cause of asthma. But the precise host response that triggers fungal allergic airway inflammation remains unclear. We found that CD11c+ DCs and CD4+ T cells are essential for development of airway inflammation in mice when repeatedly exposed to inhaled spores. To delinate which DC subsets are mediating fungal allergic inflammation we undertook single cell RNAseq of DCs isolated from the lungs of mice exposed to fungal spores. This identified precise subsets altered upon spore exposure and following targeted removal identified distinct DC subsets (Mgl2+ cDC2s) that are essential for fungal allergic airway inflammation.
2024-12-04 | E-MTAB-13740 | biostudies-arrayexpress
Project description:Group 2 innate lymphoid cells (ILC2s) have emerged as critical mediators in driving allergic airway inflammation. Here, we identified angiotensin (Ang) II as a positive regulator of ILC2s. ILC2s expressed higher levels of the Ang II receptor AT1a, and colocalized with lung epithelial cells expressing angiotensinogen. Administration of Ang II significantly enhanced ILC2 responses both in vivo and in vitro, which were almost completely abrogated in AT1a-deficient mice. Deletion of AT1a or pharmacological inhibition of the Ang II - AT1 axis resulted in a remarkable remission of airway inflammation. The regulation of ILC2s by Ang II was cell-intrinsic and dependent on interleukin (IL)-33, and was associated with marked changes in transcriptional profiling and upregulation of ERK1/2 phosphorylation. Furthermore, higher levels of plasma Ang II correlated positively with the abundance of circulating ILC2s as well as disease severity in asthmatic patients. These observations reveal a critical role for Ang II in regulating ILC2 responses and airway inflammation.
2021-12-13 | GSE190617 | GEO