DJ-1 governs airway progenitor cell/eosinophil interactions to promote allergic inflammation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE207415 | GEO | 2023/12/01
REPOSITORIES: GEO
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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:Allergic diseases are becoming a global health crisis. Individuals harboring loss-of-function variants in transforming growth factor beta receptor (TGFbR) have an increased prevalence of allergic disease, but the mechanisms responsible are poorly understood. We demonstrate that mice harboring a variant identified in patients spontaneously develop disease that clinically, immunologically, histologically, and transcriptionally recapitulates eosinophilic esophagitis, a condition characterized by allergic inflammation in the esophagus. Diminished TGFbR signaling impairs epithelial cell maturation, resulting in local expression of inflammatory mediators that drive accumulation and activation of eosinophils, mast cells, T cells, and innate lymphoid cells. Our work reveals a fundamental, non-redundant, cell-intrinsic role for TGFbR signaling in epithelial cells needed to maintain immune homeostasis and prevent allergic inflammation, independent of barrier function or adaptive immune tolerance. Moreover, we demonstrate that epithelial dysfunction alone is sufficient to initiate and perpetuate allergic inflammation, which has implications for the prevention and treatment of allergic diseases.
2023-01-15 | GSE193756 | GEO
Project description:Mast cells, basophils, and eosinophils play an important role in allergic disorders as effector cells. These cells secrete abundant serine proteases as well as chemical mediators and cytokines. Various serine proteases including SLPI are also important for to regulate an allergic response in these effector cells, although the expression profiles and functions of these proteases still remain unclear. We carried out DNA microarrays to clarify the role of SLPI in allergic responses.
2017-12-21 | GSE87638 | GEO
Project description:Comparative analysis of gene expression in murine sinonasal mucosa in wild-type and CC10-knockout littermates with allergic eosinophilic chronic rhinosinusitis. The data provide a comprehensive overview of genes expressed in the mouse sinonasal mucosa and show that the expression of several known and unidentified genes is modified by disruption of the CC10 gene. Total RNA isolated from sinonasal mucosae of 6- to 8-week-old mice, C57BL/6 strain, was used for this comparison. Three groups: wild-type control, wild-type with allergic eosinophilic chronic rhinosinusitis, and CC10-knockout with allergic eosinophilic chronic rhinosinusitis.
2010-12-01 | E-GEOD-20969 | biostudies-arrayexpress
Project description:DJ-1 is a causative gene for a familial form of Parkinson disease. DJ-1 deficient mice develop progressive behavioral abnormalities in gaits and forearm grip strength are hypoactive. The mechanisms under the activity are not fully known. Here we show that DJ-1 is critical for disuse- induced skeletal muscle atrophy. Firstly, DJ-1 expression is positively correlated with muscle mass in human, and is decreased in atrophy muscle of immobilization mice and aged human. Secondly, DJ-1-deficient muscles are dystrophic, as well as impaired in activities and oxidative capacity. In disuse-atrophic condition, skeletal muscle specific-DJ-1 knockout mice show less cross section area (CSA) and more central nuclei than control mice. Thirdly, biochemical analysis indicates that these changes are due to enhanced activation of FoxO1, and subsequent upregulation of atrogenes. Finally, the inhibitor of DJ-1, compound 23, can mimic the effects of DJ-1 ablation in vivo. Our results illuminate that skeletal muscle DJ-1 has an unexpected role in the regulation of catabolic signals from mechanical stimulation, providing a therapeutic target for muscle-wasting diseases.
2023-12-12 | GSE216408 | 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:our data showed that the absence of DJ-1 had no adverse effects on proliferation, differentiation, and oxidative stress responses of human stem cells such as hNSCs and hMSCs as well as hVECs, suggesting that loss of DJ-1 function alone is insufficient to disrupt the homeostasis of these human cells. In addition, we found that CHCHD2 was upregulated upon DJ-1 deficiency, which may account for the absence of severe phenotypes in various types of DJ-1-deficient cells. For the first time, our study revealed the 'see-saw' expression pattern of two Parkinson’s disease-associated genes, providing potential clues for understanding the mechanisms of DJ-1- and CHCHD2-associated Parkinson’s disease.
2019-09-05 | GSE136834 | GEO
Project description:Decline in immune function during aging increases susceptibility to different aging related diseases. However, the underlying molecular mechanisms, especially the genetic factors contributing to imbalance of naïve/memory T-cell subpopulations, still remain largely elusive. Here we show that loss of DJ-1 encoded by PARK7/DJ-1, causing early-onset familial Parkinson’s disease (PD), unexpectedly diminished signs of immunoaging in T-cell compartments of both human and mice. Compared with two gender-matched unaffected siblings of similar ages, the index PD patient with DJ-1 deficiency showed a decline in many critical immunoaging features, including almost doubled non-senescent T cells. The observation was further consolidated by the results in 45-week-old DJ-1 knockout mice. Our data demonstrated that DJ-1 regulates several immunoaging features via hematopoietic-intrinsic and naïve-CD8-intrinsic mechanisms. Mechanistically, DJ-1 depletion reduced oxidative phosphorylation (OXPHOS) and impaired TCR sensitivity in naïve CD8 T cells at a young age, accumulatively leading to a reduced aging process in T-cell compartments in older mice. Our finding suggests an unrecognized critical role of DJ-1 in regulating immunoaging, discovering a potent target to interfere with immunoaging- and aging-associated diseases.
2022-01-17 | GSE173904 | GEO
Project description:We aimed to identify a reprogramming factor in mammalian oocytes. DJ-1 is one candidate gene of the factor. Inhibition of DJ-1 function in nuclear transfer embryos affected developmental abilities. The downstream effect of this DJ-1 inhibition was examined using microarrays.
2011-04-07 | GSE18104 | GEO
Project description:Mast cells are known to be the key players in type I hypersensitivity reactions in humans and mice. They are critically involved in the development of allergic rhinitis, allergic asthma and systemic anaphylaxis. In this study we investigated the role of the transcriptional regulator MAZR in mast cells by comparing the expression profile of mast cells generated from wild-type (MazrF/F) and MAZR-deficient (MazrF/F x Vav-iCre) bone marrow cells. Our results from the array data demonstrate that MAZR acts preferentially as a transcriptional repressor in mast cells.
2013-10-18 | E-MTAB-1816 | biostudies-arrayexpress