The inflammatory skin disease map: an interactive computational resource focused on psoriasis and atopic dermatitis molecular mechanisms.

A TR(I)P to Pruritus Research: Role of TRPV3 in Inflammation and Itch

Soluble FAS Ligand: A Discriminating Feature between Drug-Induced Skin Eruptions and Viral Exanthemas

Preclinical Evaluation of Local JAK1 and JAK2 Inhibition in Cutaneous Inflammation

Epigenetic factors involved in the pathophysiology of inflammatory skin diseases

Autoimmune encephalitis associated with autoimmune blistering diseases: A case series and retrospective review

IL-17C is a member of the IL-17 family of cytokines. The expression of IL-17C has been demonstrated to be strongly induced by TNFα in human keratinocytes, and recently the level of IL-17C was found to be increased in the inflammatory skin disease psoriasis. However, little is known about the molecular mechanisms involved in the regulation of IL-17C. Here, we show that pretreatment of cultured human keratinocytes with the inhibitor of κB kinase 2 inhibitor, SC-514, resulted in a significant reduction in both IL-17C mRNA and protein expression, indicating the significance of this pathway in the regulation of IL-17C. NF-κB binding sites were identified upstream from the IL-17C gene, and by electrophoretic mobility shift assay NF-κB was shown to bind to all three identified binding sites. Moreover, NF-κB binding to these sites was inducible by TNFα. Supershift analysis revealed binding of the NF-κB subunits p65 and p50 to all three NF-κB binding sites. To determine the contribution of NF-κB in IL-17C expression, we conducted luciferase gene reporter experiments and demonstrated that a 3204-bp promoter fragment of IL-17C containing three putative NF-κB binding sites was strongly activated by TNFα. Interestingly, mutations of the three NF-κB binding sites revealed that one specific NF-κB binding site was crucial for the TNFα-mediated IL-17C induction because mutation of this specific site completely abolished TNFα-induced IL-17C promoter activation. We conclude that the activation of NF-κB (p65/p50) is crucial for the TNFα-induced stimulation of IL-17C expression in human keratinocytes.

Inflammatory dermatologic diseases have long been viewed as a “skin limited” disease process. Current literature on inflammatory dermatologic diseases investigates their relationship and influence on thromboembolic states and thromboembolic complications and the understanding of their pathophysiology and molecular mechanisms.Studies specifically discuss known inflammatory skin diseases including alopecia areata, vitiligo, psoriasis, hidradenitis suppurativa, atopic dermatitis, chronic spontaneous urticaria, and autoimmune bullous diseases, and their effects on systemic inflammation, associated cardiovascular comorbidities, and thromboembolic or hypercoagulable states. The limited current literature shows potential for links between inflammatory skin diseases and hypercoagulable states. Biomarkers such as F1 + 2, D-dimer, eosinophilic cationic protein, and PAI-1 are currently being studied to outline the mechanisms connecting inflammatory skin disease to the coagulation system. Further study and larger amounts of data are needed to draw definitive conclusions, especially when interpreting biomarkers alone such as PAI-1.The mechanisms, rates of systemic inflammation, and clinical outcomes of traditionally “skin limited” inflammatory diseases remain chronically understudied in dermatology. Many organ systems have well established connections between inflammatory disease and hypercoagulable states, but there are significant gaps in the literature regarding skin diseases. There is a significant need for comprehensive investigation of molecular mechanisms behind inflammatory dermatologic disease and hypercoagulability, how hypercoagulability effects clinical outcomes, and proper intervention to optimize patient outcomes.

Bidirectional relationship between atopic dermatitis and inflammatory bowel disease: A systematic review and meta-analysis

The tryptophan metabolism enzyme L-kynureninase is a novel inflammatory factor in psoriasis and other inflammatory diseases

Do not be alarmed: understanding IL33-ST2 signalling in wound repair.

The Indian Ayurvedic physicians knew the concept of inflammation dating back to 1500 BC. The continuous progress in the immunology of inflammation has explained its undiscovered mechanisms. For example, the discovery of Toll-like receptor 4 (TLR4) in humans (1997) has revolutionized the field of infection biology and innate immunity. The laboratory mice have shown twelve TLRs and express TLR10 (CD290) as a disrupted pseudogene, and humans have ten functional TLRs. Now, it is well established that TLRs play a significant role in different infectious and inflammatory diseases. Skin inflammation and other associated inflammatory diseases, including atopic dermatitis (AD), acne vulgaris, and psoriasis, along with many skin cancers are major health problems all over the world. The continuous development in the immunopathogenesis of inflammatory skin diseases has opened the window of opportunity for TLRs in studying their role. Hence, the manuscript explores the role of different TLRs in the pathogenesis of skin inflammation and associated inflammatory diseases. The article starts with the concept of inflammation, its origin, and the impact of TLRs discovery on infection and inflammation biology. The subsequent section describes the burden of skin-associated inflammatory diseases worldwide and the effect of the geographical habitat of people affecting it. The third section explains skin as an immune organ and explains the expression of different TLRs on different skin cells, including keratinocytes, Langerhans cells (LCs), skin fibroblasts, and melanocytes. The fourth section describes the impact of TLRs on these cells in different skin-inflammatory conditions, including acne vulgaris, AD, psoriasis, and skin cancers. The article also discusses the use of different TLR-based therapeutic approaches as specific to these inflammatory skin diseases.

Dysbiosis in the skin microbiome is closely associated with various inflammatory skin diseases. However, current research on the causal relationship between the skin microbiome and inflammatory skin diseases lacks comprehensive and detailed investigation. We used a two-sample Mendelian randomization (MR) approach to explore associations between the skin microbiome and seven inflammatory skin diseases, including acne, atopic dermatitis, erysipelas, vitiligo, psoriasis, rosacea, and urticaria. The GWAS summary data for the skin microbiome was derived from 647 participants in two German population-based cohorts, and for the inflammatory skin diseases, they were sourced from the FinnGen consortium. Our primary MR analysis method was the inverse variance weighted (IVW) method, complemented by alternatives like MR-Egger regression, weighted median estimation, and constrained maximum likelihood. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, and MR-PRESSO outlier detection, were conducted to validate and stabilize our findings. We identified significant causal relationships between the skin microbiome and seven inflammatory skin diseases: acne, atopic dermatitis, erysipelas, vitiligo, psoriasis, rosacea, and urticaria, with 7, 6, 9, 1, 7, 4, and 7 respective causal relationships for each disease. These relationships comprise 20 protective and 14 risk causal relationships. We applied the false discovery rate correction to these results. Sensitivity analysis revealed no significant pleiotropy or heterogeneity. Our study revealed both beneficial and detrimental causal relationships between diverse skin microbiota and inflammatory skin diseases. Additionally, the ecological niche of the skin microbiome was crucial to its functional impact. This research provided new insights into how skin microbiota impacted skin diseases and the development of therapeutic strategies.

Atopic dermatitis (AD), psoriasis (PS), and contact dermatitis (CD) are common skin diseases, characterized by barrier disruption and systemic inflammation, with unique epidermal signatures and common inflammatory pathways identified by transcriptomic profiling. This study profiled proteomic signatures in serum from subjects with AD, PS, and CD compared with healthy controls (HC). Identify unique proteomic signatures to distinguish between inflammatory diseases with similar epidermal disruption and overlapping epithelial inflammation. Sera from 20 subjects with moderate to severe AD, 10 subjects with CD, 12 subjects with moderate to severe PS, 10 subjects with both AD and CD, and 10 HC with no history of skin disease was analysed using high-throughput proteomic analysis that detects expression of 1129 protein targets. Protein expression was compared between disease and HC, and across diseases for statistical significance (fold change≥1.5 and false discovery rate≤0.05), to identify unique proteomic signatures for each disease. Complement C5A anaphylatoxin (C5A), lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), ILT-4, C-C motif ligand 18 (PARC), and sialic acid-binding Ig-like lectin 14 (SIG14) were significantly modulated in all three diseases compared with HC. We identified unique signatures for AD (Immunoglobulin E (IgE), thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC)), CD (10 proteins), and PS (kynureninase (KYNU)). Proteomic profiling in subjects with both AD and CD identified additional dysregulated proteins compared with subjects with either condition alone, indicating an exacerbated inflammation reaction. Unique sera proteomic signatures may distinguish between inflammatory skin diseases despite similar epidermal barrier disruption and epithelial inflammation. This may provide insight into disease pathogenesis, diagnosis, and therapeutic intervention in difficult-to-treat subjects.

Inflammatory skin diseases include a variety of skin diseases, such as seborrheic dermatitis, acne, atopic dermatitis, psoriasis and so on, which are more common and tend to have a significant impact on patients' quality of life. Inflammatory skin diseases often result in physical or psychological distress; however, the pathogenesis of these diseases have not been clearly elucidated. Many factors are involved in the pathogenesis of inflammatory skin diseases, including heredity, environment, immunity, epidermal barrier, mental disorders, infection and so on. In recent years, skin microbiota has been shown to play an important role in inflammatory skin diseases. To elaborate on the specific mechanisms of inflammatory skin diseases induced by microbiota dysbiosis. We introduce the function and influence of skin microbiota in inflammatory skin diseases from the following aspects: Immunity, epigenetics, epidermal barrier and treatment. Skin microbiota can affect many aspects of the host, such as Immunity, epigenetics, epidermal barrier, and it plays an important role in the pathogenesis of inflammatory skin diseases. Skin microbiota is extremely important for maintaining the health of skin and the dysbiosis of skin microbiota is an important pathogenesis of inflammatory skin diseases.

Distinct Roles for Neutrophils and Dendritic Cells in Inflammation and Autoimmunity in motheaten Mice