Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva [Nanostring]
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PROVIDER: PRJNA793899 | ENA |
REPOSITORIES: ENA
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Project description:Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva
| PRJNA802978 | ENA
Project description:Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva [Sequencing]
| PRJNA802979 | ENA
Project description:Purpose: To investigate the mechanism for developing dry eye disease in the Pinkie mouse strain with a loss of function RXR mutation. Methods: Measures of dry eye disease were assessed in the cornea and conjunctiva. Expression profiling by single-cell RNA sequencing (scRNA-seq)was performed to compare gene expression in conjunctival immune cells. Conjunctival immune cells were immunophenotyped by flow cytometry and confocal microscopy. Activity of RXR ligand 9-cis retinoic acid (RA) was evaluated in cultured monocytes and T cells. Results: Compared to wild type (WT) C57BL/6, Pinkie has increased signs of dry eye disease, including corneal barrier disruption, conjunctival cornification and goblet cell loss, and corneal vascularization, opacification, and ulceration with aging. scRNA-seq of conjunctival immune cells identified T cells as the predominant IL-17 expressing population in both strains and there is a 4-fold increased percentage of T cells in Pinkie. Compared to WT, significantly increased expression of IL-17a and IL-17f in conventional T cells and IL-17f in T cells was found in Pinkie. Flow cytometry and immunostaining revealed an increased number of IL-17+ T cells in Pinkie. Tear concentration of the IL-17 inducer IL-23 is significantly higher in Pinkie. 9-cis RA treatment suppresses stimulated IL-17 production by T and stimulatory activity of monocyte supernatant on T cell IL-17 production. Compared to WT bone marrow chimeras, Pinkie chimeras have increased IL-17+ T cells in the conjunctiva after desiccating stress and anti-IL-17 treatment suppresses dry eye induced corneal MMP-9 production/activity and conjunctival goblet cell loss. Conclusion: These findings indicate that RXR suppresses generation of dry eye disease inducing T17 cells in the conjunctiva and identifies RXR as a potential therapeutic target in dry eye.
2022-01-04 | GSE192960 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-02-03 | GSE195962 | GEO
Project description:Cultured monocytes were divided into three groups; 1) a control group 2) monocytes treated with LPS (0.5 ug/ml) for 6 hours 3) monocytes pre-treated with 100nM 9CisRA for 1 hour followed by LPS treatment for 6 hours.
2022-02-05 | GSE195961 | GEO
Project description:The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye
| PRJNA718236 | ENA
Project description:The pathophysiology of dry eye disease (DED) remains largely unknown, accounting in part for the lack of successful treatments. We explored the pathophysiology of DED using a rabbit model of chronic DED induced with 3 weekly injections of Concanavalin A into the periorbital lacrimal glands. The transcriptome of full-thickness's conjunctival tissue from rabbits with DED and from normal controls was determined using microarrays and, as needed, confirmatory real-time polymerase chain reactions. Results were subjected to bioinformatic analysis. DED induced large-scale changes in gene transcription involving 5,184 genes (22% of the total). Differentially expressed genes could be segregated into: functional modules and clusters; altered pathways; functionally linked genes; and groups of individual genes of known or suspected pathophysiological relevance to DED. A common feature of these subgroups is the breadth and magnitude of the changes that encompass ocular immunology and essentially all aspects of cell biology. Prominent changes concerned innate and adaptive immune responses; ocular surface inflammation; at least 25 significantly altered signaling pathways; a large number of chemokines; cell cycle; and apoptosis. Comparison of our findings to the limited extant transcriptomic data from DED patients associated with either Sjogren's syndrome or non-Sjogren's etiologies revealed a significant correlation between human and rabbit DED transcriptomes. Our data, establishing the large-scale transcriptomic changes of DED and their potential similarity to the human, underscore the enormous complexity of DED; establish a robust animal model of DED; will help expand our understanding of its pathophysiology; and could guide the development of successful therapeutic strategies.
| S-EPMC8321226 | biostudies-literature
Project description:Rabbit Dry Eye Diesease model induced with 3 weekly injections of Concanavalin A into the periorbital lacrimal glands Male Dutch-Belted rabbits. The pathophysiology of dry eye disease (DED) remains largely unknown, accounting in part for the lack of successful treatments. The transcriptome of full-thickness’s conjunctival tissue from rabbits with DED and from normal controls was determined using microarrays. DED induced large-scale changes in gene transcription involving 5,184 genes (22% of the total). Differentially expressed genes could be segregated into: functional modules and clusters; altered pathways; functionally linked genes; and groups of individual genes of known or suspected pathophysiological relevance to DED. A common feature of these subgroups is the breadth and magnitude of the changes that encompass ocular immunology and essentially all aspects of cell biology. Prominent changes concerned innate and adaptive immune responses; ocular surface inflammation; at least 25 significantly altered signaling pathways; a large number of chemokines; cell cycle; and apoptosis. Comparison of our findings to the limited extant transcriptomic data from DED patients associated with either Sjogren’s syndrome or non-Sjogren’s etiologies revealed a significant correlation between human and rabbit DED transcriptomes. Our data, establishing the large-scale transcriptomic changes of DED and their potential similarity to the human, underscore the enormous complexity of DED; establish a robust animal model of DED; will help expand our understanding of its pathophysiology; and could guide the development of successful therapeutic strategies.
2021-03-30 | GSE171043 | GEO
Project description:PurposeDry eye is closely related to the activation and proliferation of immune cells, especially T cells. However, the determination of the preferential T-cell clonotypes is technically challenging. This study aimed to investigate the characterization of T-cell receptor (TCR) repertoire in the conjunctiva during dry eye.MethodsA desiccating stress animal model was established using C57/BL6 mice (8-10 weeks, female). After 7 days of stress stimulation, the slit-lamp image and Oregon-green-dextran staining were used to evaluate the ocular surface injury. Periodic acid-Schiff staining was used to measure the number of goblet cells. Flow cytometry was used to detect the activation and proliferation of T cells in the conjunctiva and cervical lymph nodes. Next-generation sequencing was used to detect the αβ TCR repertoire of the conjunctiva.ResultsThe αβ TCR diversity increased significantly in the dry eye group, including the higher CDR3 amino acid length, marked gene usage on TCR V and J gene segments, extensive V(D)J recombination, and distinct CDR3 aa motifs. More important, several T-cell clonotypes were uniquely identified in dry eye. Furthermore, these perturbed rearrangements were reversed after glucocorticoid administration.ConclusionsA comprehensive analysis of the αβ TCR repertoire in the conjunctiva of the dry eye mouse model was performed. Data in this study contributed significantly to the research on dry eye pathogenesis by demonstrating the TCR gene distribution and disease-specific TCR signatures. This study further provided some potential predictive T-cell biomarkers for future studies.
| S-EPMC10007900 | biostudies-literature
Project description:Comparison of endogenous gene expression differences between pterygium and conjunctiva tissues RNA from donor-matched pterygium and conjunctiva tissues obtained from four patients were evaluated for differences in gene expression
2016-06-23 | E-GEOD-83627 | biostudies-arrayexpress