Project description:Cutaneous lupus erythematosus (CLE) is a disfiguring disease that can exist as an independent entity or as a manifestation of systemic lupus erythematosus (SLE) where up to 70% of patients experience lesions during their disease course. Subacute CLE (sCLE) is an inflammatory lesion with associated erythema in papulosquamous or annular formations. Typically, sCLE does not scar but depigmentation can occur. Importantly, sCLE is associated with a higher progression to SLE. Discoid lesions (DLE) are often circular and frequently lead to alopecia and scar formation. sCLE lesions have a higher propensity for photoprovocation and a more robust inflammatory infiltrate following ultraviolet (UV) B exposure. The pathogenic mechanisms which govern the differences between DLE and sCLE remain poorly defined, and this is reflected by the refractory nature of cutaneous lesions to usual lupus therapies. In this study, we evaluated the transcriptional profiles of 26 DLE and 23 sCLE biopsies and compared them to control skin and to each other in order to develop a comprehensive understanding of the similarities and differences between these two clinical subtypes.
Project description:Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus. Despite its high frequency in systemic lupus in addition to cases without extracutaneous manifestations, targeted treatments for DLE are lacking, likely because of a dearth of knowledge of the molecular landscape of DLE skin. Here, we profiled the transcriptome of DLE skin in order to identify signaling pathways and cellular signatures that may be targeted for treatment purposes. Further comparison of the DLE transcriptome with that of psoriasis, a useful reference given our extensive knowledge of molecular pathways in this disease, provided a framework to identify potential therapeutic targets. Although a growing body of data support a role for IL-17 and T helper type 17 (Th17) cells in systemic lupus, we show a relative enrichment of IFN-γ-associated genes without that for IL-17-associated genes in DLE. Extraction of T cells from the skin of DLE patients identified a predominance of IFN-γ-producing Th1 cells and an absence of IL-17-producing Th17 cells, complementing the results from whole-skin transcriptomic analyses. These data therefore support investigations into treatments for DLE that target Th1 cells or the IFN-γ signaling pathway. Comparison of transcriptomes between skin conditions
Project description:Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus. Despite its high frequency in systemic lupus in addition to cases without extracutaneous manifestations, targeted treatments for DLE are lacking, likely because of a dearth of knowledge of the molecular landscape of DLE skin. Here, we profiled the transcriptome of DLE skin in order to identify signaling pathways and cellular signatures that may be targeted for treatment purposes. Further comparison of the DLE transcriptome with that of psoriasis, a useful reference given our extensive knowledge of molecular pathways in this disease, provided a framework to identify potential therapeutic targets. Although a growing body of data support a role for IL-17 and T helper type 17 (Th17) cells in systemic lupus, we show a relative enrichment of IFN-γ-associated genes without that for IL-17-associated genes in DLE. Extraction of T cells from the skin of DLE patients identified a predominance of IFN-γ-producing Th1 cells and an absence of IL-17-producing Th17 cells, complementing the results from whole-skin transcriptomic analyses. These data therefore support investigations into treatments for DLE that target Th1 cells or the IFN-γ signaling pathway.
Project description:Lupus, a server and complex autoimmune disease, is clinically divided into cutaneous lupus erythematosus (CLE) which featured in skin damage, and systemic lupus erythematosus (SLE) which characterized in systemic multi-organ damage. The distinction of these two types of lupus is widely unknown. Here, we collected 23 skin biopsies of healthy control(HC), DLE (discoid lupus erythematosus, a main type of CLE) and SLE, separated epidermis and dermis and performed single cell RNA sequencing through microfluidics based 10x genomics system. Our results demonstrated larger numbers of immune cells infiltrated in skin lesions of DLE than SLE, which may help to distinguish them. Then, non-immune cells such as keratinocytes and fibroblasts were showed functions like immune cells. Moreover, ISGs(interferon stimulated genes), HSP70 coding genes were found to be overexpressed in multi expanded subclusters. Some biological progresses such as autophagy and neutrophil activation were enriched in expanded subclusters.
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).
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.
Project description:To investigate changes in immune cell signatures in the transcriptomes of DLE lesional skin versus normal skin Comparison of the transcriptome of DLE lesional skin with normal skin
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.