Activated T cells secrete extracellular vesicles in the allergic airway that enhance eosinophil viability
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ABSTRACT:
PROVIDER: PRJNA1064163 | ENA |
REPOSITORIES: ENA
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Project description:T cells are not only central orchestrators of immune responses, but they drive tissue pathology in many inflammatory diseases. In allergic asthma, the activation of CD4+ T helper cells in response to allergens drives chronic type 2 lung inflammation characterized by the recruitment of eosinophils. Given the emerging roles of extracellular vesicles (EVs) as mediators of cell-to-cell communication, we hypothesized that T cells would secrete EVs in the lung to regulate the local inflammatory response. Using T cell specific membrane tagging and single vesicle flow cytometry, we found that T cell EVs are secreted into lung lining fluid during allergic inflammation in a mouse model of asthma. Functionally, EVs secreted by polarized T helper type 2 (Th2) cells promote eosinophil survival in vitro. This effect is only seen with EVs collected from Th2 cells activated through the T cell receptor. Activated Th2 cell EVs promote eosinophil survival by a surface-cargo dependent anti-apoptotic mechanism, inducing pro-survival and activation gene expression programs in these target cells. In vivo, activated Th2 cell EVs prolong eosinophilia in the lung after administration into the airways during allergic inflammation. Together, this study adds to emerging literature linking cellular activation state to EV function and supports a role for T cell EVs in enhancing tissue inflammation.
2025-07-03 | GSE253180 | GEO
Project description:Understanding the metabolic mechanisms driving eosinophil differentiation in allergic airway inflammation is imperative for developing effective asthma therapies. Despite iron's well-established involvement in various cellular processes, its role in eosinophil differentiation remains elusive. This study observed elevated intracellular iron levels during eosinophil differentiation in the context of allergic airway inflammation. Through experiments involving iron-related compounds and specific diets, we demonstrated iron's indispensable role in promoting eosinophil differentiation, both in vitro and in vivo. Remarkably, an iron chelator effectively suppressed eosinophil differentiation and alleviated allergic airway inflammation. Mechanistically, iron maintains mitochondrial metabolic activities, mTORC1 signaling, and the expression of transcription factors that enforce eosinophil differentiation. Notably, iron influx rewires specific metabolic shifts in Krebs cycle, with succinate promoting eosinophil differentiation. Overall, this study highlights the significance of understanding the regulatory role of iron and underlying metabolic mechanisms in eosinophil differentiation, providing potential metabolic intervention strategies for asthma treatment.
2025-06-19 | GSE260684 | GEO
Project description:Background DJ-1 is an antioxidant protein known to regulate mast cell mediated allergic response, but its role in airway eosinophilic interactions and allergic inflammation is not known. Objective The aim of this study was to investigate the role of DJ-1 in airway eosinophilic inflammation in vitro and in vivo. Methods Ovalbumin-induced airway allergic inflammation was established in mice. ELISA was adopted to analyze DJ-1 and cytokine levels in mouse bronchoalveolar lavage fluid. Transcriptional profiling of mouse lung tissues was conducted by single-cell RNA sequencing technology. The role of DJ-1 in the differentiation of airway progenitor cells into goblet cells was examined by organoid cultures, immunofluorescence staining, quantitative PCR, and cell transplantation in normal, DJ-1 knockout (KO), or conditional DJ-1 KO mice. Results We observed that DJ-1 was increased in the lung tissues of ovalbumin-sensitized and challenged mice. DJ-1 KO mice exhibited reduced airway eosinophil infiltration and goblet cell differentiation. Mechanistically, we discovered that eosinophil-club cell interactions are reduced in the absence of DJ-1. Organoid cultures indicated that eosinophils impair the proliferative potential of club cells. Intratracheal transplantation of DJ-1-deficient eosinophils suppresses airway goblet cell differentiation. Loss of DJ-1 inhibits the metabolism of arachidonic acid into cysteinyl leukotrienes in eosinophils while these secreted metabolites promote airway goblet cell fate in organoid cultures and in vivo. Conclusion DJ-1-mediated interactions between airway epithelial progenitor cells and immune cells are essential in controlling airway goblet cell metaplasia and eosinophilia. Blockade of the DJ-1 pathway is protective against airway allergic inflammation.
2022-12-21 | GSE203079 | GEO
Project description:Iron Drives Eosinophil Differentiation in Allergic Airway Inflammation through Mitochondrial Metabolic Adaptation
| PRJNA1082691 | ENA
Project description:DJ-1 governs airway progenitor cell/eosinophil interactions to promote allergic inflammation
| PRJNA838489 | ENA
Project description:DJ-1 is an antioxidant protein known to regulate mast cell mediated allergic response, but its role in airway eosinophilic interactions and allergic inflammation is not known.
2023-12-01 | GSE207415 | GEO
Project description:<p>Eosinophils are the predominant immune cells implicated in the pathogenesis of asthma, highlighting the need for strategies to mitigate their effects. While previous studies have indicated a potential relationship between lysosomes and eosinophils, the precise role of lysosomes in eosinophil activation during asthma remains insufficiently understood. In this study, we demonstrated that lysosomal acidity and cathepsin L (CTSL) activity in eosinophils were elevated in asthmatic patients and mouse models. Genetic deletion or pharmacological inhibition of CTSL in eosinophils significantly attenuated allergic airway inflammation in vivo and suppressed eosinophil activation in vitro. CTSL in eosinophils promoted type 2 immune responses by upregulating arginase 1 (ARG1) expression and interacting with it, thereby enhancing ARG1 activity and altering arginine metabolism during eosinophil activation. This metabolic shift led to increased production of ornithine, which exacerbated inflammatory processes. Furthermore, lysosomal acidity and CTSL activity correlated with disease severity in asthmatic patients. Our findings reveal that lysosomal acidity and CTSL facilitate eosinophil activation through arginine metabolism, thereby promoting allergic airway inflammation.</p>
2025-09-15 | MTBLS13001 | MetaboLights
Project description:MicroRNA have been implicated in the differentiation and control of eosinophilia in allergic inflammation, however, a detailed investigation of miRNA expression patterns employed during differentiation has not yet been performed [35-37]. The aim of our study is to explore miRNA expression profiling and analysis in silico in order to improve our understanding of the factors and circuits that are involved in the regulation eosinophil growth and differentiation.
2014-08-01 | E-MTAB-2442 | biostudies-arrayexpress
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:As opposed to their well-characterized contributions to inflammatory processes, tissue eosinophils are now also thought to contribute to immune homeostasis at mucosal sites such as the gut. Yet, whether such steady-state eosinophils exist in the lung is currently unclear. In this project, we identified and characterized lung resident eosinophil and also studied what happen to these cell during a mouse model of allergic inflammation (House dust mite (HDM) exact administrations). We compared the transcriptional profile of lung resident eosinophil from naive mice (rEOS ss) or from HDM-treated mice (rEOS i) and of inflammatory eosinophil (iEOS) from HDM-treated mice.
2016-06-07 | E-MTAB-4084 | biostudies-arrayexpress