Publications by authors named "Johann Gudjonsson"

Objective: Cutaneous lupus erythematosus (CLE) is an inflammatory skin manifestation of systemic lupus erythematosus (SLE). Type I interferons (IFNs) promote inflammatory responses and are elevated in CLE lesions. We recently reported that CLE lesions are frequently colonized with Staphylococcus aureus (S.

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Background: Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of interferon gamma (IFN)-γ, a cytokine implicated in the pathogenesis of LP.

Methods: In this phase II trial, twelve patients with cutaneous LP received baricitinib 2 mg daily for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre- and post-treatment samples.

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Macrophage transition from an inflammatory to reparative phenotype after tissue injury is controlled by epigenetic enzymes that regulate inflammatory gene expression. We have previously identified that the histone methyltransferase SETDB2 in macrophages drives tissue repair by repressing NF-κB-mediated inflammation. Complementary ATAC-Seq and RNA-Seq of wound macrophages isolated from mice deficient in SETDB2 in myeloid cells revealed that SETDB2 suppresses the inflammatory gene program by inhibiting chromatin accessibility at NF-κB-dependent gene promoters.

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The expressions of long noncoding RNAs (lncRNAs) and their roles in epidermal differentiation have been previously defined using bulk RNA sequencing. Despite their tissue-specific expression profiles, most lncRNAs are not well-annotated at the single-cell level. In this study, we evaluated the use of single-cell RNA sequencing to profile and characterize lncRNAs using data from 6 patients with psoriasis with paired uninvolved and lesional psoriatic skin.

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  • Grover disease is a skin condition characterized by blistering caused by the breakdown of connections between skin cells, with its causes still unknown and no FDA-approved treatment available.
  • Research has shown that B-RAF inhibitors used in cancer treatment can paradoxically lead to Grover disease by causing hyperactivation of ERK, which disrupts skin cell cohesion.
  • The study suggests that inhibiting MEK can prevent the onset of Grover disease by controlling ERK activation, indicating a potential therapeutic approach that could benefit both Grover disease and similar genetic conditions like Darier disease.
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Immune cell-mediated inflammation is important in normal tissue regeneration but can be pathologic in diabetic wounds. Limited literature exists on the role of CD4+ T cells in normal or diabetic wound repair; however, the imbalance of CD4+ Th17/Tregs has been found to promote inflammation in other diabetic tissues. Here, using human tissue and murine transgenic models, we identified that the histone methyltransferase Mixed-lineage-leukemia-1 (MLL1) directly regulates the Th17 transcription factor RORγ via an H3K4me3 mechanism and increases expression of Notch receptors and downstream Notch signaling.

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  • Exposure to ultraviolet (UV) light is a known trigger for inflammation in systemic lupus erythematosus (SLE), but the specific cells involved in this response and how UV exposure interacts with interferons are not fully understood.
  • This study utilized a murine model of lupus, comparing responses in NZM2328 mice and iNZM mice with a type I interferon receptor knockout, as well as wild-type BALB/c mice, to investigate the effects of different UV treatments.
  • Findings showed that myeloid cells, particularly neutrophils and monocyte-derived dendritic cells, play a key role in the inflammatory response to UV exposure in lupus-prone mice, emphasizing the potential for targeting type I interferons and
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Desmosomes are intercellular junctions that mediate cell-cell adhesion and are essential for maintaining tissue integrity. Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease caused by autoantibodies (IgG) targeting desmoglein 3 (Dsg3), a desmosomal cadherin. PV autoantibodies cause desmosome disassembly and loss of cell-cell adhesion, but the molecular signaling pathways that regulate these processes are not fully understood.

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Purpose: Current therapies for proliferative diabetic retinopathy (PDR) do not specifically target VEGF-independent, cell-type-specific processes that lead to vision loss, such as inflammatory pathways. This study aimed to identify targetable cell types and corresponding signaling pathways by elucidating the single-cell landscape of the vitreous of patients with PDR.

Design: Case series.

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  • Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis, and the study investigates the role of soluble CD13 (sCD13) and its signaling through the bradykinin receptor B1 (B1R) in SSc pathogenesis.
  • Researchers found elevated levels of CD13, B1R, and MMP14 in skin from SSc patients, which contributed to fibrosis through signaling pathways activated by TGF-β and sCD13.
  • The study concludes that targeting the sCD13-B1R axis could represent a novel and effective therapeutic strategy for treating skin fibrosis in SSc.
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Purpose: Clinical next-generation sequencing is an effective approach for identifying pathogenic sequence variants that are medically actionable for participants and families but are not associated with the participant's primary diagnosis. These variants are called secondary findings (SFs). According to the literature, there is no report of the types and frequencies of SFs in a large pediatric cohort that includes substantial African-American participants.

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  • Palmoplantar pustulosis (PPP), palmoplantar psoriasis (palmPP), and dyshidrotic palmoplantar eczema (DPE) are inflammatory skin conditions that can be difficult to distinguish from one another due to similar clinical presentations.
  • Recent RNA sequencing studies of these conditions revealed overlapping inflammatory responses, particularly involving proinflammatory cytokines and immune processes, alongside unique features for each disease.
  • The findings suggest that current classifications based on clinical symptoms may be insufficient, emphasizing the need for a better molecular understanding of these diseases to improve diagnosis and treatment.
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Long-standing hypertension (HTN) affects multiple organ systems and leads to pathologic arterial remodeling, which is driven largely by smooth muscle cell (SMC) plasticity. Although genome wide association studies (GWAS) have identified numerous variants associated with changes in blood pressure in humans, only a small percentage of these variants actually cause HTN. In order to identify relevant genes important in SMC function in HTN, we screened three separate human GWAS and Mendelian randomization studies to identify SNPs located within non-coding gene regions, focusing on genes encoding epigenetic enzymes, as these have been recently identified to control SMC fate in cardiovascular disease.

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  • - Sweet's syndrome is an inflammatory skin disease involving the influx of neutrophils in the skin, and it features a strong interferon response that's not seen in other similar skin conditions.
  • - Research using advanced techniques on skin samples found that various cells, especially fibroblasts, display genes activated by interferons, suggesting they respond to inflammation.
  • - The study highlights specific fibroblast populations in Sweet's syndrome that are located at different distances from neutrophils, indicating their potential role in the disease's development by responding to type I interferons.
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  • Pityriasis rubra pilaris (PRP) is a rare skin condition with unclear causes, but recent research identified IL-1β as a crucial factor in its development.
  • Treatment with IL-1 antagonists like anakinra and canakinumab led to significant improvements in patients, including reduced skin lesions within a few weeks.
  • The findings suggest that PRP could be redefined as an autoinflammatory keratinization disorder, highlighting the need for further clinical trials to test the effectiveness of targeting IL-1β in treatment.
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Atopic dermatitis (AD) is a highly heritable and common inflammatory skin condition affecting children and adults worldwide. Multi-ancestry approaches to AD genetic association studies are poised to boost power to detect genetic signal and identify ancestry-specific loci contributing to AD risk. Here, we present a multi-ancestry GWAS meta-analysis of twelve AD cohorts from five ancestral populations totaling 56,146 cases and 602,280 controls.

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Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens.

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Macrophage (Mφ) plasticity is critical for normal wound repair; however, in type 2 diabetic wounds, Mφs persist in a low-grade inflammatory state that prevents the resolution of wound inflammation. Increased NLRP3 inflammasome activity has been shown in diabetic wound Mφs; however, the molecular mechanisms regulating NLRP3 expression and activity are unclear. Here, we identified that diabetic wound keratinocytes induce Nlrp3 gene expression in wound Mφs through IL-1 receptor-mediated signaling, resulting in enhanced inflammasome activation in the presence of pathogen-associated molecular patterns and damage-associated molecular patterns.

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  • Inflammatory epithelial diseases involve a complex dysregulation of both immune and epithelial cells, making it unclear how these cells manage their high metabolic needs.
  • Research using single-cell and spatial transcriptomics found that HIF1α, influenced by IL-17 signaling, plays a key role in the remodeling of psoriatic epithelial tissues and is critical for glycolysis.
  • Experimental results from both human samples and murine models showed that blocking HIF1α or related pathways significantly reduced pathology linked to skin inflammation, highlighting a connection between metabolism and immune responses in such diseases.
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Grover disease is an acquired dermatologic disorder characterized by pruritic vesicular and eroded skin lesions. While its pathologic features are well-defined, including impaired cohesion of epidermal keratinocytes, the etiology of Grover disease remains unclear and it lacks any FDA-approved therapy. Interestingly, drug-induced Grover disease occurs in patients treated with B-RAF inhibitors that can paradoxically activate C-RAF and the downstream kinase MEK.

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As the circadian clock regulates fundamental biological processes, disrupted clocks are often observed in patients and diseased tissues. Determining the circadian time of the patient or the tissue of focus is essential in circadian medicine and research. Here we present tauFisher, a computational pipeline that accurately predicts circadian time from a single transcriptomic sample by finding correlations between rhythmic genes within the sample.

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