Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA377232 | ENA |
REPOSITORIES: ENA
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Project description:Cutaneous lupus erythematosus (CLE) is a photosensitive autoimmune disease characterized by a strong type-I-interferon (IFN) associated inflammation. Keratinocytes are known to determine the interface-dermatitis-pattern in CLE by production of proinflammatory cytokines in the lower epidermis. These cytokines drive a cytotoxic anti-epithelial immune response resulting in keratinocytic cell death and release of endogenous nucleic acids (eNA). We hypothesized that these eNA (RNA- and DNA-motifs) have the capacity to activate innate immune pathways in keratinocytes via pathogen-recognition-receptors (PRR). Gene expression analyses revealed an excessive activation of innate immune response pathways with strong expression of IFN-regulated cytokines in CLE skin lesions. Cultured keratinocytes produce large amounts of these cytokines in response to stimulation of PRR with eNA. UV-stimulation enhances the immunogenicity of eNA and induces CLE-like skin lesions in knockout mice lacking the cytosolic DNase TREX1. Our results provide evidence for a pathogenetic role of endogenous nucleic acids in CLE. They are released within the cytotoxic inflammation along the dermo-epidermal junction and have the capacity to drive the LE-typical inflammation. UV-irradiation supports this inflammation by generation of highly immunostimulatory DNA motifs (8-OHG). These findings explain the photosensitivity of lupus patients and identify pathways of the innate immune system as targets for future therapies.
2017-03-01 | GSE95474 | GEO
Project description:We performed gene expression analysis on cultured Th0, Th1 and Th2 cells pre-injection, and on enriched T cells from lesional skin of cutaneous lupus erythematosus (CLE) mice post-injection, to compare differences in transcription that could predict skin tropism and flare
2022-06-01 | GSE185355 | GEO
Project description:Lesional skin biopsies were taken from patients with active, untreated lupus skin disease (chronic discoid lupus erythematosus, CDLE, n=6; subacute cutaneous lupus erythematosus, SCLE, n=5). Healthy control specimens (HC) were obtained from healthy skin of 5 patients undergoing plastic surgery. In every case, two 4mm punch biopsies were taken. One was flash-frozen in liquid nitrogen and afterwards processed for mRNA isolation. The second biopsy was fixed in 5% formalin solution overnight, and was proceeded for histological investigation.The one-color Agilent 60-mer oligo microarray (Agilent, Santa Clara, CA) was used for gene expression analyses. Statistical analyses were performed using the Agilent Feature Extraction Software⢠and the Rosetta Resolver⢠gene expression data analysis system. The presented gene list (Table S1) includes normalized sample/ control log10-ratios (expression > 2-fold enhanced, p<0.01).
2017-02-24 | E-MTAB-5542 | biostudies-arrayexpress
Project description:Cutaneous lupus erythematosus (CLE) is a disfiguring and poorly understood condition frequently associated with systemic lupus. Studies to date suggest that non-lesional keratinocytes play a role in disease predisposition, but this has not been investigated in a comprehensive manner or in the context of other cell populations. To investigate CLE immunopathogenesis, normal-appearing skin, lesional skin, and circulating immune cells from lupus patients were analyzed via integrated single-cell RNA-sequencing and spatial-seq. We demonstrate that normal-appearing skin of lupus patients represents a type I interferon-rich, ‘prelesional’ environment that skews gene transcription in all major skin cell types and dramatically distorts cell-cell communication. Further, we show that lupus-enriched CD16+ dendritic cells undergo robust interferon education in the skin, thereby gaining pro-inflammatory phenotypes. Together, our data provide a comprehensive characterization of lesional and non-lesional skin in lupus and identify a role for skin education of CD16+ dendritic cells in CLE pathogenesis.
2022-03-25 | GSE186476 | GEO
Project description:We performed spatial transcriptomics on a case series of different clinical subtypes of cutaneous lupus erythematosus including acute cutaneous lupus erythematosus (malar rash, systemic lupus erythematosus). Our goals were to (1) determine which differentially expressed genes (DEGs) could be attributed to specific cell populations in specific locations within the tissue, (2) determine if spatial transcriptomics could better distinguish between CLE clinical subtypes than bulk RNA approaches and (3) examine potential cell-cell communication pathways within the skin lesions.
2021-10-01 | GSE182825 | GEO
Project description:We performed a comparative immunology case study of client-owned dogs to determine if immune and skin gene expression profiles in spontaneous canine cutaneous lupus erythematosus mirror those observed in human cutaneous lupus.
2022-03-23 | GSE160260 | GEO
Project description:Systemic lupus erythematosus is progressive, immune complex-mediated autoimmune disease targeting numerous organs. A central feature of the disease is the development of antibodies against nuclear components, including DNA. Antibodies against double-stranded DNA are so characteristic of this disease that their detection constitutes one of the criteria for diagnosis. We examined the formation of immune complexes on the surface of autoantigen microarrays incubated in the sera of 39 inactive and 22 active lupus patients and of 31 control subjects. Three different kinds of nucleic acids, dsDNA, ssDNA and RNA were used as antigens, along with chromatin (nucleosomal extract) and several other reference molecules. The composition with respect to IgG, IgM and complement components C3 and C4 was determined. We find that while IgM and C4 are physiological components of immune complexes formed from nucleic acids, both IgG and C3 are extremely characteristic of lupus patients. Complement C4 deposition changes were not consistent: these increased on ssDNA and RNA, decreased on chromatin and did not change significantly on dsDNA. The presence of IgG and C3 in the immune complexes formed from different nucleic acids was characteristic for both active and inactive lupus patients. Receiver-operating curve statistics indicate that C3 deposition measurements can improve the efficiency of identification of inactive lupus patients. These observations reveal the complexity of immune profile changes accompanying SLE. C3, IgM, C4 and IgG binding in 92 human serum samples were examined using custom-made protein arrays
2012-09-30 | E-GEOD-26768 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus is progressive, immune complex-mediated autoimmune disease targeting numerous organs. A central feature of the disease is the development of antibodies against nuclear components, including DNA. Antibodies against double-stranded DNA are so characteristic of this disease that their detection constitutes one of the criteria for diagnosis. We examined the formation of immune complexes on the surface of autoantigen microarrays incubated in the sera of 39 inactive and 22 active lupus patients and of 31 control subjects. Three different kinds of nucleic acids, dsDNA, ssDNA and RNA were used as antigens, along with chromatin (nucleosomal extract) and several other reference molecules. The composition with respect to IgG, IgM and complement components C3 and C4 was determined. We find that while IgM and C4 are physiological components of immune complexes formed from nucleic acids, both IgG and C3 are extremely characteristic of lupus patients. Complement C4 deposition changes were not consistent: these increased on ssDNA and RNA, decreased on chromatin and did not change significantly on dsDNA. The presence of IgG and C3 in the immune complexes formed from different nucleic acids was characteristic for both active and inactive lupus patients. Receiver-operating curve statistics indicate that C3 deposition measurements can improve the efficiency of identification of inactive lupus patients. These observations reveal the complexity of immune profile changes accompanying SLE.
2012-09-30 | GSE26768 | GEO
Project description:Aicardi-Goutières syndrome (AGS) is a severe childhood inflammatory disorder that shows clinical and genetic overlap with systemic lupus erythematosus (SLE). AGS is thought to arise from the accumulation of incompletely metabolized endogenous nucleic acid species owing to mutations in nucleic acid degrading enzymes TREX1 (AGS1), RNase H2 (AGS2, 3 and 4) and SAMHD1 (AGS5). However, the identity and source of such immunogenic nucleic acid species remain undefined. Using genome-wide approaches, we show that fibroblasts from AGS patients with AGS1-5 mutations are burdened by excessive loads of RNA:DNA hybrids. Using MethylC-seq, we show that AGS fibroblasts display pronounced and global loss of DNA methylation and demonstrate that AGS-specific RNA:DNA hybrids often occur within DNA hypomethylated regions. Altogether, our data suggest that RNA:DNA hybrids may represent a common immunogenic form of nucleic acids in AGS and provide the first evidence of epigenetic perturbations in AGS, furthering the links between AGS and SLE.
2015-07-17 | GSE57353 | GEO