CD163 macrophages display mixed polarizations in discoid lupus skin
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE72535 | GEO | 2015/09/01
SECONDARY ACCESSION(S): PRJNA294289
REPOSITORIES: GEO
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Project description:Transcriptome of discoid lupus erythematosus (DLE) skin
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Project description:This is a phase I randomized, double-blind, placebo-controlled crossover study which sought to evaluate a single dose of AMG 811, an anti-IFNγ antibody, in patients with DLE. The patients in sequence 1 received AMG 811 followed by placebo, while those in sequence 2 received placebo followed by AMG 811. Pharmacodynamic end points included global transcriptional analyses of lesional and nonlesional skin, IFNγ blockade signature (IGBS) transcriptional scores in the skin and blood, keratinocyte IFNγ RNA scores, and serum levels of CXCL10 protein
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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
2013-11-18 | E-GEOD-52471 | biostudies-arrayexpress
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.
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Project description:Cutaneous lupus erythematosus (CLE) is an autoimmune disease that localizes to the skin and is known to contain elevated glycosaminoglycans (GAGs) on Hale’s stain of skin biopsy specimens. Recently, different GAG species have been shown to have distinct effects on the recruitment and activation of immune cells and stimulation of cytokine production (Taylor and Gallo, FASEB, 2006; 20: 9-22). Thus, we speculate that the elevated GAGs observed in CLE play a role in the local inflammatory process that produces skin lesions in these patients. In order to further investigate a molecular basis for the elevated expression of these GAGs in CLE skin lesions, we would like to determine the gene expression profiles of GAG synthesis, degradation, and modifier genes in lesional and non-lesional skin samples from CLE patients and compare to those from healthy controls. A microarray approach will give us a broader understanding of the genetic regulation of the expression of various GAG species in CLE skin. We will then be able to target future quantitative gene expression experiments by real-time RT-PCR to the genes that are shown to be involved in CLE. In order to accomplish our goal, we would like to examine the GAG gene expression profiles of DLE, TLE, and SCLE subtypes due to the differences in CS and HA staining that we found among these subtypes. Since HA and CS are elevated in DLE and HA in TLE, but not in SCLE, the SCLE samples will also serve as an internal control. We would like to examine both lesional and non-lesional skin biopsies to determine if CLE skin prior to developing a lesion is different at the genetic level from healthy control skin and how it changes once a lesion does develop. We will separate the dermis from the epidermis of the skin biopsies and extract RNA just from the dermis to enrich for dermal fibroblast RNA. We aim to submit four patient biopsies per subtype as well as four samples from healthy control skin for comparison. This number is necessary in order to account for the biologic variability among different patients. We would submit more samples per subtype but are limited by availability of patients in clinic. Thus, we will have a total of 28 samples to submit for microarray. This study design will allow us to analyze the GAG gene expression profiles among different CLE subtypes and enable us to identify which GAc
2011-06-14 | E-GEOD-29938 | biostudies-arrayexpress
Project description:This is a phase I randomized, double-blind, placebo-controlled crossover study which sought to evaluate a single dose of AMG 811, an anti-IFNγ antibody, in patients with DLE. The patients in sequence 1 received AMG 811 followed by placebo, while those in sequence 2 received placebo followed by AMG 811. Pharmacodynamic end points included global transcriptional analyses of lesional and nonlesional skin, IFNγ blockade signature (IGBS) transcriptional scores in the skin and blood, keratinocyte IFNγ RNA scores, and serum levels of CXCL10 protein
2017-06-23 | GSE100430 | GEO
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.
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Project description:To determine the transcriptional profile associated with macrophage polarization to M1 or M2, we cultured macrophages derived from monocytes for 7 days and treated them with IFNg, IL-4, TNF, LPS, and LPS+IFNg (n=7). Psoriasis lesional and non-lesional skin biopsies were included (n=5 pairs).
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