Eosinophils in Lung Allograft
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ABSTRACT:
PROVIDER: PRJNA925858 | ENA |
REPOSITORIES: ENA
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Project description:While the function of many leukocytes in transplant biology has been well defined, the role of eosinophils is controversial and remains poorly explored. Conflicting data exist regarding eosinophils’ role in alloimmunity based on context and organ type. Due to their prevalence in the lung, and their defined role in other pulmonary pathology such as asthma, we set out to explore the role of eosinophils in the long-term maintenance of the lung allograft. We noted that depletion of eosinophils results in the generation of donor-specific antibodies. Eosinophil depletion increased memory B cell, plasma cell, and antibody secreting cell differentiation and resulted in de novo-generation of follicular germinal centers. Germinal center formation depended on the expansion of CD4+Foxp3-Bcl6+CXCR5+PD1+ T follicular helper cells (Tfh) which increase in number after eosinophil depletion. Mechanistically, we demonstrate that eosinophils prevent Tfh generation by acting as the dominant source of IFN-γ in an established lung allograft, thus facilitating Th1 rather than Tfh polarization of naïve CD4+ T cells. Our data thus describe a unique and previously unknown role for eosinophils in maintaining allograft tolerance and suggests that indiscriminate administration of eosinophil-lytic corticosteroids for treatment of acute cellular rejection may inadvertently promote humoral alloimmunity.
2025-01-14 | GSE223268 | GEO
Project description:Eosinophils were isolated from the lungs of mice that were resting naïve or 7 or 30 days post-transplant with costimulatory blockade
2025-01-14 | GSE223352 | GEO
Project description:The eosinophil transcriptome analysis indicated a robust transcription change in eosinophils following allergen challenge in the lung. Eosinophils were FACS-sorted from Saline or OVA challenged lung with high purity and then subjected to genome-wide RNA microarray
2014-05-19 | E-GEOD-57757 | biostudies-arrayexpress
Project description:Purpose: we aimed to characterized eosinophils in the murine model of asthma Methods: Eosinophils were sorted from the lung of naïve and and HDM-induced asthma mice. There after RNA was extracted from the sorted eosinophils and subjected to RNAseq. Results:we demonstrated that resident lung eosinophils require IL-5 for their survival and that the expression of Siglec-F, is regulated by IL-5 . Conclusion: Our data suggest that the distinct eosinophil populations in the asthmatic lung represent a continuum of activation states rather than distinct eosinophil subsets.
2023-04-17 | GSE203225 | GEO
Project description:Eosinophils promote lung emphysema via CTSL
| PRJNA996546 | ENA
Project description:Lung allograft rejection results in the accumulation of low molecular weight hyaluronic acid (LMW-HA), which further propagates inflammation and tissue injury. We have previously shown that therapeutic lymphangiogenesis in a murine model of lung allograft rejection reduced tissue LMW-HA and was associated with improved transplant outcomes. Herein we investigated the use of 4-Methylumbelliferone (4-MU), a known inhibitor of HA synthesis, to alleviate acute allograft rejection in a murine model of lung transplantation. We found that treating mice with 4-MU from day 20-30 post-transplant was sufficient to significantly improve outcomes, characterized by a reduction in T-cell mediated lung inflammation, LMW-HA content and improved pathology scores. In vitro, 4-MU directly attenuated activation, proliferation, and differentiation of naïve CD4+ T-cells into Th1 cells. As 4-MU has already been demonstrated to be safe for human use, we believe examining 4-MU for the treatment of acute lung allograft rejection may be of clinical significance.
2021-12-15 | GSE183142 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE15345: Expression of survivin in lung eosinophils is associated with pathology in a mouse model of allergic asthma 1 GSE15414: Expression of survivin in lung eosinophils is associated with pathology in a mouse model of allergic asthma 2 Refer to individual Series
2010-05-18 | E-GEOD-15429 | biostudies-arrayexpress
Project description:The eosinophil transcriptome analysis indicated a robust transcription change in eosinophils following allergen challenge in the lung.
2014-05-19 | GSE57757 | GEO
Project description:The recognition of the immune system as a key component of the tumor microenvironment (TME) led to promising therapeutics. Since such therapies benefit only subsets of patients, understanding the activities of immune cells in the TME is required. Eosinophils are an integral part of the TME especially in mucosal tumors. Nonetheless, their role in the TME and the environmental cues that direct their activities are largely unknown, especially in metastasis. We report that breast cancer-driven lung metastasis is characterized by resident and recruited eosinophils. Eosinophil recruitment to the metastatic lung was regulated by G protein coupled receptor signaling but independent of CCR3. Functionally, eosinophils promoted lymphocyte-mediated anti tumor immunity. Transcriptome and proteomic analyses identified the TME rather than intrinsic differences between eosinophil subsets as a key instructing factor directing anti tumorigenic eosinophil activities. Specifically, TNF-a/IFN-g-activated eosinophils facilitated CD4+ and CD8+ T cell infiltration and promoted anti-tumor immunity. Collectively, we identify a mechanism by which the TME entrains eosinophils to adopt anti-tumorigenic properties, which may lead to the development of eosinophil-targeted therapeutics.
2021-07-27 | PXD027596 | Pride
Project description:Patients with chronic obstructive pulmonary disease (COPD) having higher blood eosinophil levels exhibit worse lung function and more severe emphysema, implying the potential role of eosinophils in emphysema development. However, the specific mechanism underlying eosinophil-mediated emphysema development is not fully elucidated. In this study, single-cell RNA sequencing was used to identify eosinophil subgroups in mouse models of asthma and emphysema and analyze their functions. Analysis of the accumulated eosinophils revealed differential transcriptomes between the mouse lungs of elastase-induced emphysema and ovalbumin-induced asthma., Eosinophil depletion alleviated elastase-induced emphysema. Notably, eosinophil-derived cathepsin L (CTSL) degraded the extracellular matrix (ECM), causing emphysema in the pulmonary tissue. Eosinophils were positively correlated with serum CTSL levels, which were increased in patients with emphysema than in those without emphysema. Collectively, these results suggest that CTSL expression in eosinophils plays an important role in ECM degradation and remodeling and is related to emphysema in patients with COPD. Therefore, eosinophil-derived CTSL may serve as a potential therapeutic target for patients with emphysema.
2023-10-17 | GSE237749 | GEO