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A pathogenic CD4 T cell phenotype in experimental uveitis shares common features with other immune mediated inflammatory diseases

ABSTRACT: Experimental autoimmune uveoretinitis, a mouse model of ocular autoimmunity, was induced by immunization with the uveitogenic peptide IRBP1-20. 26 days after disease induction, CD4 T cells were purified by cell sorting for RNAseq.

ORGANISM(S): Mus musculus

PROVIDER: GSE289820 | GEO | 2025/06/16

REPOSITORIES: GEO

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A pathogenic CD4 T cell phenotype in experimental uveitis shares common features with other immune mediated inflammatory diseases [EAU]

Project description:Experimental autoimmune uveoretinitis, a mouse model of ocular autoimmunity, was induced by the transfer of allelically marked T cells. Thirteen days after transfer, CD4 cells were sorted from spleens and individual eyes and processed using the SMART-Seq v4 Ultra Low Input RNA kit. Samples were classified as: transferred cells from the eye, transferred cells from the spleen, endogenous cells from the eye, endogenous cells from the spleen. Analysis of differential gene expression revealed an extended pathogenic phenotype that shared common features with other models of autoimmunity.

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A pathogenic CD4 T cell phenotype in experimental uveitis shares common features with other immune mediated inflammatory diseases

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A pathogenic CD4 T cell phenotype in experimental uveitis shares common features with other immune mediated inflammatory diseases [EAU]

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Single-cell transcriptomic analysis of retinal immune regulation and blood-retinal barrier function during experimental autoimmune uveitis

Project description:Uveitis is characterised by breakdown of the blood-retinal barrier (BRB), allowing infiltration of immune cells that mediate intraocular inflammation, which can lead to irreversible damage of the neuroretina and the loss of sight. Treatment of uveitis relies heavily on corticosteroids and systemic immunosuppression due to limited understanding of the molecular immune interactions that underpin ocular immune homeostasis. By performing single-cell transcriptomic analysis of whole dissociated mouse retinas with experimental autoimmune uveitis (EAU) versus healthy control, we gained an unbiased appreciation of the immune interactions that drive retinal inflammation in a model of posterior uveitis.

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Intra-ocular dendritic cells characterize HLA-B27-associated acute anterior uveitis

Project description:Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. uveitis associated with the HLA haplotype B27 (HLA-B27) is a common subtype of uveitis and a prototypical ocular immune-mediated disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations. Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27 positive (n=3) and negative (n=2) anterior uveitis and an infectious endophthalmitis control (n=1) by combining single cell RNA-sequencing with flow cytometry and protein analysis. Ocular cell infiltrates consisted primarily of lymphocytes in both subtypes of uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27 positive uveitis exclusively featured a plasmacytoid and classical dendritic cells (cDC) infiltrate. Moreover, cDCs were central in predicted local cell-cell communication. This suggests a unique pattern of ocular leukocyte infiltration in HLA-B27 positive uveitis with relevance of dendritic cells.

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Experimental and clinical assessment of angiogenesis-related parameters inpatients with juvenile idiopathic arthritis-associated uveitis

Project description:Introduction: In chronic and treatment-resistant cases of juvenile idiopathic arthritis-associated uveitis (JIAU), alterations of the iris vasculature may be observed clinically. We sought to investigate this phenomenon by combining clinical and laboratory analyses. Methods: Iris tissue (IT), aqueous humor (AH) and serum samples from patients with clinically inactive JIAU (n=30) or acute anterior uveitis (AAU; n=18), and primary open angle glaucoma (POAG; n=20) were obtained during ocular surgery. Samples were analyzed by RNA-sequencing (RNA-Seq), qRT-PCR, liquid chromatography, high–definition mass spectrometry technique (LC-MS), Western-Blot (WB), and LEGENDplex analysis. Pattern of iris vasculature in JIAU patients was assessed qualitatively via fluorescein and indocyanine green angiography (FLA/ICGA). Results: RNA-Seq of IT showed significantly differential expression (DE) of 136 genes between JIAU and POAG, of which 15 were associated with angiogenesis. qRT-PCR, performed to validate RNA-Seq results, showed significant upregulation of the angiogenesis-related genes Kdr, Angpt-1, Tie-1, Tie-2 and Mmrn2 in IT (JIAU vs POAG). LC-MS of IT revealed a total number of 56 DE proteins (JIAU vs POAG), of which asporin, lumican and decorin were associated with angiogenesis and showed increased (p>0.05) expression on WB analysis. LEGENDplex analysis showed upregulation of ANGPT-2 in AH from JIAU compared to AAU and POAG, whereas VEGF was upregulated in AAU. Iris vascular leakage, hypoperfusion and neovascularization were observed by FLA/ICGA in JIAU patients with treatment-refractory complicated course of uveitis. Conclusion: Angiogenesis-related genes and proteins are upregulated in the iris tissue of JIAU patients, correlating with increased vascular permeability, hypoperfusion, and neovascularization of the anterior uveal tissue in chronic and complicated JIAU.

2021-04-09 | GSE171745 | GEO

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