Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury [scRNA-seq]
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PROVIDER: PRJNA1107338 | ENA |
REPOSITORIES: ENA
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Project description:Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury [ChIP-seq]
| PRJNA1107339 | ENA
Project description:Sepsis, a worldwide health crisis, is notorious for its high mortality rate, often attributed to the development of acute lung injury. The direct migration of intestinal immune cells to the lung as a mediator of acute lung injury remains unclear. Our study unveiled a process where cecal ligation and puncture-induced sepsis prompted a migration of γδT cells from the small intestine to the lung, subsequently triggering an overwhelming inflammatory response dominated by IL-17A.
2024-06-14 | GSE266493 | GEO
Project description:Sepsis, a worldwide health crisis, is notorious for its high mortality rate, often attributed to the development of acute lung injury. The direct migration of intestinal immune cells to the lung as a mediator of acute lung injury remains unclear. Our study unveiled a process where cecal ligation and puncture-induced sepsis prompted a migration of γδT cells from the small intestine to the lung, subsequently triggering an overwhelming inflammatory response dominated by IL-17A.
2024-06-14 | GSE266492 | GEO
Project description:Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44+ Ly6C- IL-7Rhigh CD8low cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/β-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.
| S-EPMC11306781 | biostudies-literature
Project description:Sepsis is a severe global health issue with high mortality rates, and sepsis-associated encephalopathy (SAE) further exacerbates this risk. While recent studies have shown the migration of gut immune cells to the lungs after sepsis, their impact on the central nervous system remains unclear. Our research demonstrates that sepsis could induce the migration of IL-7Rhigh CD8low γδ T17 cells from the small intestine to the meninges, where they secrete IL-17A, impairing mitochondrial function in microglia and activating the cGAS-STING-C1q pathway. This process is accompanied by inhibited ubiquitination of STING at the K150 site, resulting in STING accumulation and increased release of C1q-tagged hippocampal synapses, which are subsequently pruned by activated microglia. Importantly, 4-Octyl itaconate mitigates the excessive synaptic pruning by inhibiting γδ T17 cell migration and promoting STING ubiquitination, thereby alleviating SAE. Our findings reveal a novel mechanism of synaptic pruning by microglia via the cGAS-STING-C1q pathway, emphasize the critical role of gut-derived γδ T17 cell migration to the meninges in SAE, and highlight the importance of STING ubiquitination in modulating C1q-mediated excessive synaptic pruning.
2024-10-28 | PXD057241 |
Project description:Here, we investigated γδ T cells in a longitudinal cohort of preterm neonates during the first year of life. Our data reveal dynamic postnatal maturation patterns of γδ T cell subsets, which are largely age-dependent. We report on the expansion of fetal-derived γδ T cells in preterm neonates with sepsis. Single cell transcriptome analyses identified HLA-DRhigh and CD83+ γδ T cells in neonatal sepsis.
2024-05-08 | GSE245131 | GEO
Project description:The following CGH experiments were conducted on four sectors (S1-S4) from a single primary ductal carcinoma tumor (T17) using the Sector-Ploidy-Profiling (SPP) Approach. SPP involves macro-dissecting the tumor, flow-sorting nuclei by differences in total genomic DNA content and profiling the genome of the tumor subpopulations.
2009-07-10 | GSE16665 | GEO
Project description:The following CGH experiments were conducted on four sectors (S1-S4) from a single primary ductal carcinoma tumor (T17) using the Sector-Ploidy-Profiling (SPP) Approach. SPP involves macro-dissecting the tumor, flow-sorting nuclei by differences in total genomic DNA content and profiling the genome of the tumor subpopulations. The genomic DNA from each tumor subpopulation was labeled with Cy5 and hybridized to an 390K Rubble-Rep ROMA Microarray. A normal reference male fibroblast was labeled with Cy3 as a control. Samples were cohybridize to the same single microarray.
2010-05-16 | E-GEOD-16665 | biostudies-arrayexpress
Project description:γδ-T lymphocytes are cells of the innate immune system exerting potent natural cytotoxicity against bacteria, viruses and tumours. This ability, coupled with their negligible alloreactivity, makes them attractive for adoptive immunotherapy approaches. To achieve a cell product suitable for clinical use, a protocol offering the possibility to generate and expand high numbers of polyclonal γδ-T cells is required. In this study, we designed a robust protocol to either manually or automatically expand high numbers of functional polyclonal memory γδ-T cells under good manufacturing practice conditions, with the additional possibility of gene-modification to improve anti-tumour activity, proving the feasibility of establishing an allogeneic “third-party T-cell bank” for off-the-shelf use. Engineered artificial antigen-presenting cells (aAPCs) expressing CD86/41BBL/CD40L and the cytomegalovirus (CMV)-antigen-pp65 were used for γδ-T cell production. The presence of CMV-pp65 and CD40L proved to be crucial for expansion of the memory Vδ1 subpopulation. To allow clinical translation and guarantee patient safety, aAPCs were stably transduced with an inducible suicide gene. The proposed cell product represents an attractive therapeutic option endowed with broad clinical applications, including treatment of viral infections in highly immunocompromised patients, treatment of aggressive malignancies refractory to conventional approaches and, ultimately, innovative platform for development of off-the-shelf CAR-T-cell products.
2019-11-18 | PXD015506 | Pride
Project description:Antigen-presenting aged neutrophils induce CD4+ T cells to exacerbate inflammation in sepsis
| PRJNA950025 | ENA