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Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE195962 | GEO | 2022/02/03

REPOSITORIES: GEO

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Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva [Sequencing]

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

Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva [Nanostring]

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

Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva

Project description:Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva

| PRJNA802978 | ENA

Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva [Sequencing]

Project description:Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva [Sequencing]

| PRJNA802979 | ENA

Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva [Nanostring]

Project description:Reduced RXRa signaling increases dry eye disease inducing gdT17 cells in the conjunctiva [Nanostring]

| PRJNA793899 | ENA

The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye

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