Common Chronic Inflammatory Disease Research Articles

Evaluation of skin barrier function based on skin dermoscopic features in patients with rosacea.

Evaluation of skin barrier function based on skin dermoscopic features in patients with rosacea.

Updates in psoriasis diagnosis and treatment status in China: results from the National Psoriasis Center Registry.

Updates in psoriasis diagnosis and treatment status in China: results from the National Psoriasis Center Registry.

Overview of Atopic Dermatitis in Different Ethnic Groups.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a high prevalence worldwide, including countries from Asia, Africa, and Latin America, and in different ethnic groups. In recent years, more attention has been placed on the heterogeneity of AD associated with multiple factors, including a patient's ethnic background, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineates differences in AD among racial groups. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, but very rarely in Africans. Th2 hyperactivation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal, whereas African Americans show a strong Th2/Th22 signature and an absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity of AD may hold important therapeutic implications as a patient's genetic predisposition may affect treatment response and, thereby, a tailored strategy that better targets the dominant immunologic pathways in each ethnic subgroup may be envisaged. Nevertheless, white patients with AD represent the largest ethnicity enrolled and tested in clinical trials and the most treated in a real-world setting, limiting investigations about safety and efficacy across different ethnicities. The purpose of this review is to describe the heterogeneity in the pathophysiology of AD across ethnicities and its potential therapeutic implications.

Subgingival instrumentation for the treatment of periodontitis

Periodontal disease is the most common chronic inflammatory non-communicable disease in the human population. It is estimated that severe periodontitis affects 11% of the world’s population, with prevalence increasing with age. Subgingival instrumentation refers to all non-surgical procedures, either performed by hand (i.e., curettes) or with power-driven instruments (i.e., sonic/ultrasonic devices).

NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes

Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK’772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK’772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis.

Study on Intestinal Flora and Asthma: Knowledge Graph Analysis Based on CiteSpace (2001-2021).

Asthma is a common chronic inflammatory disease of the airway. Intestinal flora, a significant risk factor for asthma, has become a widespread concern in the pathogenesis of asthma. To review the literature related to intestinal flora in asthma, summarize research direction, and report trends, this study used CiteSpace to perform bibliometric statistics and analysis on the research papers of intestinal flora and asthma collected in the Web of science core collection from 2001 to 2021. Eventually, a total of 613 articles were included. The results demonstrated that research on gut flora and asthma continued to heat up, with article numbers increasing, especially in the last decade. Moreover, analysis of the keywords showed that the research topics of intestinal flora and asthma range from confirming the link between intestinal flora and asthma to investigating mechanisms and then to asthma treatment. According to the summary of research hotspots, we expand on three emerging issues that require attention in the intestinal flora and asthma research, including (regulatory T)Treg cells, probiotics, and chain fatty acid. Evidence illustrated that Treg cells play a crucial role in the pathogenesis of asthma caused by dysbiosis of the gut flora. Furthermore, in contrast to probiotic supplements, which do not reduce the risk of developing asthma, short-chain fatty acids supplements do. Overall, the research direction in the field of intestinal flora and asthma has recently evolved from macro to micro with depth broadened. As a robust scientific evaluation, our study provided a comprehensive overview of the area, particularly for research focus, which could more precisely direct scholars on future research and clinical diagnosis, therapy, and individualized prevention.

A Novel E3 Probiotics Formula Restored Gut Dysbiosis and Remodelled Gut Microbial Network and Microbiome Dysbiosis Index (MDI) in Southern Chinese Adult Psoriasis Patients.

Psoriasis is a common chronic immune-mediated inflammatory skin disease with the association of various comorbidities. Despite the introduction of highly effective biologic therapies over the past few decades, the exact trigger for an immune reaction in psoriasis is unclear. With the majority of immune cells residing in the gut, the effect of gut microbiome dysbiosis goes beyond the gastrointestinal site and may exacerbate inflammation and regulate the immune system elsewhere, including but not limited to the skin via the gut-skin axis. In order to delineate the role of the gut microbiome in Southern Chinese psoriasis patients, we performed targeted 16S rRNA sequencing and comprehensive bioinformatic analysis to compare the gut microbiome profile of 58 psoriasis patients against 49 healthy local subjects presumably with similar lifestyles. Blautia wexlerae and Parabacteroides distasonis were found to be enriched in psoriasis patients and in some of the healthy subjects, respectively. Metabolic functional pathways were predicted to be differentially abundant, with a clear shift toward SCFA synthesis in healthy subjects. The alteration of the co-occurrence network was also evident in the psoriasis group. In addition, we also profiled the gut microbiome in 52 of the 58 recruited psoriasis patients after taking 8 weeks of an orally administrated novel E3 probiotics formula (with prebiotics, probiotics and postbiotics). The Dermatological Life Quality Index (p = 0.009) and Psoriasis Area and Severity Index (p < 0.001) were significantly improved after taking 8 weeks of probiotics with no adverse effect observed. We showed that probiotics could at least partly restore gut dysbiosis via the modulation of the gut microbiome. Here, we also report the potential application of a machine learning-derived gut dysbiosis index based on a quantitative PCR panel (AUC = 0.88) to monitor gut dysbiosis in psoriasis patients. To sum up, our study suggests the gut microbial landscape differed in psoriasis patients at the genera, species, functional and network levels. Additionally, the dysbiosis index could be a cost-effective and rapid tool to monitor probiotics use in psoriasis patients.

Modern understanding of endoscopy technology at a periodontal appointment: a systematic review

Relevance. Periodontitis is a common chronic infectious and inflammatory disease. Multiple microorganisms, including periodontal pathogens in the dental biofilm, are the principal reason for inflammatory periodontal diseases. The initial stage of periodontitis treatment involves the mechanical removal of dental deposits from the tooth surface. Subgingival scaling is technically complex due to the limited visualization. An experienced clinician does not always have a chance to thoroughly treat all roo ts’ surfaces and remove all plaque and tartar.Modern technology, e.g., Perioscopy, enables illumination and visualization of periodontal pockets and their content. Thus, dental endoscopy technology practicability determination requires the study of the systematization of a large initial data array.Materials and methods. Publications were searched and studied in seven electronic databases PubMed, Google Search, Embase, Web of Science, ScienceDirect, and SciELO II eLibrary. The study reviewed the articles published from 2000 to 2022, available in full text, and assessed for relevance. The search resulted in 119 selected publications. Based on the inclusion criteria, we selected 44 articles, which included 42 clinical trials and two reviews. The study methodology meets the requirements for systematic reviews (PRISMA).Results. High-quality visualization allows for the operating field control enabling access to hard-to-reach areas and improves periodontal treatment outcomes. Closed periodontal scaling, the most commonly used non-surgical inflammatory periodontal disease treatment technique, is based on the dentist’s tactile sensations and experience. Due to the lack of visual control, even an experienced practitioner may not always effectively treat all surfaces or remove all plaque and tartar. The examination with the endoscope (Perioscopy) after the instrumentation reveals areas of tartar and biofilm remains, which may lead to further periodontal destruction and future surgical treatment. The article presents the studies proving the sufficient effectiveness of a dental endoscope for periodontal disease treatment. It is of note that the endoscope significantly increases the treatment quality in cases with deep pockets and severe periodontitis.Conclusion. Endoscopic imaging of dental deposits and pocket content indirectly reduces the risk of recurrence and complications of inflammatory periodontal diseases. The treatment of patients with moderate and severe periodontitis requires the development of algorithms for the management of such patients with the mandatory use of an endoscope.

Detection and treatment of skin infection with Staphylococcus aureus in children with atopic dermatitis

Introduction. Atopic dermatitis is a common chronic relapsing inflammatory multifactorial skin disease. Staphylococcus aureus skin colonization increases during disease outbreaks and correlates with the severity of skin symptoms. Purpose - to evaluate the effectiveness of thyrothricin gel as an adjuvant therapy in the treatment of atopic dermatitis and the influence of polymorphisms of pattern recognition receptors on the achieving a therapeutic effect. Materials and methods. This study included patients with atopic dermatitis (n=37) aged 2-18 years from the Allergy Department of the Kyiv City Children’s Clinical Hospital No. 2. Patients were devided into two groups: a group that received thyrothricin gel on the affected skin areas 2 times a day for 7 days (the Group A) and a control group (the Group B) that received only basic symptomatic therapy. SCORAD (SCORing AD) and CDLQI (Children’s Quality of Life Index in Dermatology) scores were recorded before and after treatment, side effects were recorded during the study. Skin swabs were taken in the Group A before and after treatment. Genotyping of polymorphisms rs4696480 in the TLR2 gene, rs7309123 in the Dectin-1 gene were performed using polymerase chain reaction. Results. In both groups of children, improvement was observed in 7 days after treatment (p&lt;0.001). In the Group A, the improvement in ΔSCORAD was 16.6±5.9 points, in the Group B - 8.1±4.5 points. The difference in ΔSCORAD scores between the Groups A and B was statistically significant (W=225.0, p&lt;0.001). The decrease in CDLQI score after treatment was 3.8±1.8 points in the Group A and 2.3±1.25 points in the Group B. A significant decrease in CDLQI score was demonstrated in the intervention group than in the control group after treatment (W=275.5, p=0.004). After treatment, a bacteriological examination of the skin demonstrated the eradication of Staphylococcus aureus: in the Group A, 94.4% of patients were Staphylococcus aureus-negative. Polymorphisms rs4696480 in the TLR2 gene and rs7309123 in the Dectin-1 gene did not affect the speed of achieving the therapeutic effect. Conclusions. The addition of thyrothricin to standard therapy for atopic dermatitis in children with Staphylococcus aureus infection of affected skin may provide significant clinical benefit in SCORAD and CDLQI scores. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patients was obtained for conducting the studies. No conflict of interests was declared by the author.

Impact of resveratrol supplementation on clinical parameters and inflammatory markers in patients with chronic periodontitis: a randomized clinical trail

BackgroundPeriodontitis is one of the most common chronic inflammatory diseases in the world, which affects oral health. Resveratrol is a polyphenol with therapeutic effects on the inflammation caused by periodontal pathogens. This study aimed to evaluate the impact of resveratrol supplementation on clinical parameters and inflammatory markers in patients with chronic periodontitis.MethodsIn this randomized, double-blind study, 40 chronic periodontitis patients underwent non-surgical therapy and were randomly assigned to two intervention and control groups, receiving either resveratrol supplements or a placebo for four weeks. Salivary levels of interleukin-8 (IL-8), interleukin-1β (IL-1β), and clinical parameters, including pocket depth (PD), clinical attachment level (CAL), plaque index (PI), and bleeding index (BI), were measured before and after the intervention.ResultsThe results showed that in both the case and control groups, after four weeks of using resveratrol, only plaque index (PI) was significantly different compared to the control group (P = 0.0001). However, there were no significant differences in the mean pocket depth (PD), clinical attachment loss (CAL), bleeding index (BI), and salivary levels of IL-8 and IL-1β between the two groups after the intervention.ConclusionResveratrol complement was helpful as an anti-inflammatory food supplement, along with other non-surgical periodontal treatments in chronic periodontitis patients.

Oligosaccharides of Polygonatum Cyrtonema Hua ameliorates dextran sulfate sodium-induced colitis and regulates the gut microbiota

Ulcerative colitis (UC) is one common chronic inflammatory bowel disease that causes severe side effects, and expensive treatment limits effective and sustained treatment of UC. Fructooligosaccharide was isolated from Polygonatum Cyrtonema Hua (PFOS) and exhibits anti-inflammatory effects. Therefore, we are curious whether PFOS could be used for the treatment of UC. PFOS was introduced via intragastric gavage to C57BL/6 J mice exposed to acute colitis induced by DSS. The results showed that doses of PFOS at 2 and 5 mg/kg/day alleviated the DSS-induced histopathological damage and improved intestinal barrier function. qPCR analysis revealed that PFOS exerted a significant downregulation of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and upregulation of antioxidant genes, including superoxide dismutase1 (SOD1), glutathion peroxidase2 (GPX2), and nuclear factor erythroid 2 related factor2 (Nrf2). Furthermore, PFOS suppressed the DSS-induced disruption of the mucosal barrier by downregulating MMP13. Moreover, using 16 S rRNA gene-based microbiota analysis, PFOS could selectively enhance the growth of probiotics, including Bifidobacterium, Alloprevofella, and Alistipes. Our findings indicated that PFOS attenuated DSS-induced colitis in mice, suggesting that PFOS might be used as an efficacious supplement for reducing inflammatory bowel disease.

Atopic dermatitis management with topical corticosteroids in children: own observations

Atopic dermatitis is the most common chronic inflammatory skin disease in children, that significantly affects quality of life. Clinical manifestations are genetically determined and caused by skin barrier dysfunction and development of immune reactions. Atopic dermatitis is characterized by early onset, recurrence, and presence of treatment resistant forms. It is important to prescribe treatment that controls the symptoms and reduces the risk of severe forms of this disease. Topical corticosteroids are the mainstay of atopic dermatitis management, although the prolonged treatment can lead to development of side effects. The treatment option, that has high efficacy and high profile of safety, is the basis for disease remission and overcoming corticosteroid phobia. Methylprednisolone aceponate meets all criteria for topical corticosteroids and has high efficacy and high profile of safety. It can be recommended for patients with atopic dermatitis from the age of 4 months. This paper shows up-to-date data on methylprednisolone aceponate, that confirm the optimized efficacy/safety profile and minimal local or systemic adverse effects. Recent studies demonstrated the efficacy of new Russian product – methylprednisolone aceponate (Komfoderm K).

A bioinformatics system for exploring potential targets and therapies in rheumatoid arthritis

Rheumatoid arthritis (RA), one of the most common chronic inflammatory diseases, is an autoimmune disease that causes cartilage, bone damage, and disability. RA has become a concern, affecting more than 1.5% of the global population. Immunomodulatory or anti-inflammatory targets are the lead candidates in existing clinical trials to develop RA drugs. These targets were reported to be ineffective in reducing symptoms, slowing disease progression, and causing adverse side effects. Therefore, this study focuses on addressing the continuing need for safer, more selective, and more effective treatment options for RA by identifying novel targets and therapeutic approaches. The study involves six important steps: retrieving a dataset from the Gene Expression Omnibus (GEO) database, file conversion, gene differentiation (up-regulated and downregulated), Entrez gene ID retrieval for Search Tool for the Retrieval of Interacting Genes (STRING), protein–protein interaction (PPI) network delineation via STRING, drugs identification via Drug Bank, and relationship establishment between networks and drugs via The Drug–Gene​ Interaction Database (DGIdb). Nine protein hubs, three up-regulated and six down-regulated were identified as interacting with 8 and 18 drugs, respectively. Seven protein sites have never been directly associated with RA and could serve as potential therapeutic targets. Eleven drugs were shown to interact with these seven selected protein hubs as potential therapeutics for RA. These new targets and therapies will help researchers improve the RA treatment pipeline by adding these into the pipeline and bringing successful treatment options for RA patients.

Metformin Attenuates the Inflammatory Response via the Regulation of Synovial M1 Macrophage in Osteoarthritis

Osteoarthritis (OA), the most common chronic inflammatory joint disease, is characterized by progressive cartilage degeneration, subchondral bone sclerosis, synovitis, and osteophyte formation. Metformin, a hypoglycemic agent used in the treatment of type 2 diabetes, has been evidenced to have anti-inflammatory properties to treat OA. It hampers the M1 polarization of synovial sublining macrophages, which promotes synovitis and exacerbates OA, thus lessening cartilage loss. In this study, metformin prevented the pro-inflammatory cytokines secreted by M1 macrophages, suppressed the inflammatory response of chondrocytes cultured with conditional medium (CM) from M1 macrophages, and mitigated the migration of M1 macrophages induced by interleukin-1ß (IL-1ß)-treated chondrocytes in vitro. In the meantime, metformin reduced the invasion of M1 macrophages in synovial regions brought about by the destabilization of medial meniscus (DMM) surgery in mice, and alleviated cartilage degeneration. Mechanistically, metformin regulated PI3K/AKT and downstream pathways in M1 macrophages. Overall, we demonstrated the therapeutic potential of metformin targeting synovial M1 macrophages in OA.

Machine learning-based prediction models for atopic dermatitis diagnosis and evaluation

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease seriously affecting the quality of life of patients. Reliable and accurate evaluation methods are necessary for early diagnosis and effective AD treatment. Thus, this study used machine learning (ML) to explore a novel diagnostic and therapeutic effect evaluation model for AD. Firstly, candidate model genes were screened from an integrated data set of four AD-related microarray datasets: GSE133477, GSE32924, GSE58558, and GSE107361, using Robust Rank Aggregation (RRA), and protein-protein interaction network (PPI). Next, three recognized models (REC) and three AD-associated gene models (AAG) established with LASSO, Logistic linear regression (LR), and random forest (RF) were developed and tested separately using GSE130588 and GSE99802 datasets. The results revealed that REC model of LASSO (model genes including IL7R, KRT16, CCL2, CD53, CCL18 and CCL22), REC model of LR(including IL7R, KRT16, CCL18) and AAG model of LR (including MX1, CCNB1, SERPINB13, ADAM19, CEP55, VMP1, TTC39A, and FCHSD1) accurately classified AD lesions and non-lesions based on the good AUCs (LASSO (REC):0.8761, and LR (REC and AAG):0.8302 in GSE130588; LASSO (REC): 0.7761, and LR (REC and AAG):0.8783 in GSE99802). In Dupilumab, Crisaborole, and fezakinumab-treated samples, the LASSO (REC) and LR(AAG) models were positively correlated with SCORD (Pearson correlation coefficients of 0.55 and 0.69, respectively) and negatively correlated with the treatment length. In addition, the two models also accurately predicted the infiltration of immune cells in the skin lesions and non-lesions. Therefore, the ML-based predictive model provides a new approach to predicting AD diagnosis and the therapeutic effect of AD treatment options.

Safety and Effectiveness of Magnesium Sulphate for Severe Acute Asthma Management Among Under-five Children: Systematic Review and Meta-analysis.

Asthma is the common chronic inflammatory disease affecting children. It is usually associated with airway hyper-responsiveness. Globally, the prevalence of asthma among pediatrics population varies from 10% to 30%. Its symptoms range from chronic cough to life-threatening bronchospasm. At emergency department, all patients with acute severe asthma should initially receive oxygen, nebulized β2-agonists, nebulized anticholinergic agent, and corticosteroids. Though bronchodilators act within minutes, corticosteroids may require hours. Magnesium sulphate (MgSO4) was first considered for treating asthma about 60 years ago. Several case reports were published on its usefulness in decreasing admission and endotracheal intubation. So far, evidence is conflicting to fully employ MgSO4 for asthma management in children under five. This systematic review was aimed to evaluate the effectiveness and safety of MgSO4 in the treatment of severe acute asthmatic attacks in children. A systematic and comprehensive search of literature was performed to identify controlled clinical trials conducted on IV and nebulized MgSO4 in pediatric patients with acute asthma. Data generated from three randomized clinical trials were included in the final analysis. In this analysis, intravenous MgSO4 did not improve respiratory function (RR=1.09, 95%CI: 0.81-1.45) and not safer than conventional treatment (RR=0.38, 95%CI: 0.08-1.67). Similarly, use of nebulized MgSO4 showed no significant effect on respiratory function (RR=1.05, 95%CI: 0.68-1.64) and more tolerable (RR=0.31, 95%CI: 0.14-0.68). Intravenous MgSO4 may not be superior to conventional treatment in moderate to severe acute asthma among children and neither have significant adverse effects. Similarly, nebulized MgSO4 showed no significant effect on respiratory function in moderate to severe acute asthma in children under five but it seems a safer alternative.

Molecular Basis beyond Interrelated Bone Resorption/Regeneration in Periodontal Diseases: A Concise Review.

Periodontitis is the sixth most common chronic inflammatory disease, destroying the tissues supporting the teeth. There are three distinct stages in periodontitis: infection, inflammation, and tissue destruction, where each stage has its own characteristics and hence its line of treatment. Illuminating the underlying mechanisms of alveolar bone loss is vital in the treatment of periodontitis to allow for subsequent reconstruction of the periodontium. Bone cells, including osteoclasts, osteoblasts, and bone marrow stromal cells, classically were thought to control bone destruction in periodontitis. Lately, osteocytes were found to assist in inflammation-related bone remodeling besides being able to initiate physiological bone remodeling. Furthermore, mesenchymal stem cells (MSCs) either transplanted or homed exhibit highly immunosuppressive properties, such as preventing monocytes/hematopoietic precursor differentiation and downregulating excessive release of inflammatory cytokines. In the early stages of bone regeneration, an acute inflammatory response is critical for the recruitment of MSCs, controlling their migration, and their differentiation. Later during bone remodeling, the interaction and balance between proinflammatory and anti-inflammatory cytokines could regulate MSC properties, resulting in either bone formation or bone resorption. This narrative review elaborates on the important interactions between inflammatory stimuli during periodontal diseases, bone cells, MSCs, and subsequent bone regeneration or bone resorption. Understanding these concepts will open up new possibilities for promoting bone regeneration and hindering bone loss caused by periodontal diseases.

Alterations in Brain Neural Network and Stress System in Atopic Dermatitis: Novel Therapeutic Interventions.

Atopic dermatitis is a common chronic inflammatory skin disease, with most cases experiencing skin barrier dysfunction and enhanced allergen entry, accompanied by cytokine production which evokes predominantly type-2-skewed immune responses, itch, and scratching behavior. Although intense itch and excessive scratching behavior affect progression of skin lesions, it is unclear what causes them. Data suggest that scratching behavior stimulates brain dopaminergic reward and habit learning systems, strengthening habitual scratching behavior, while nocturnal scratching behavior presumably increases locus coeruleus-noradrenergic system activity, prompting sleep disturbances. At the early stage of atopic dermatitis, increased cortisol levels, due to hypothalamic-pituitary-adrenal axis overactivation caused by such system stimulation, can induce dorsolateral prefrontal cortex disturbance with reinforcement of habitual scratching behavior and may aggravate type-2-skewed immune responses in the skin. During the later phases, whereas blunted hypothalamic-pituitary-adrenal axis function and the shift of type-2-dominated to type-1-co-dominated inflammation are induced, noradrenergic system overactivation-associated dorsolateral prefrontal cortex disruption is ongoing and responsible for itch cognitive distortion to catastrophize about itch, which leads to a vicious spiral along with habitual scratching behavior and skin lesions. Data are presented in this review indicating that while skin immune system dysfunction initiates pathologic changes in atopic dermatitis, brain neural network and stress system alterations can promote the progression of this condition. It is also suggested that cognitive distortion contributes to pathology in atopic dermatitis as with some psychiatric disorders and chronic pain. The proposed mechanistic model could lead to development of novel medications for slowing or terminating the relentless progression of this disorder. SIGNIFICANCE STATEMENT: Although conventional pharmacological interventions focusing on skin homeostasis and itch occurrence significantly attenuate clinical signs in atopic dermatitis patients, achievement of 100% improvement is less than 40% in several double-blind, randomized, placebo-controlled trials. Our model predicts that itch cognitive distortion, due to dorsolateral prefrontal cortex disturbance, can significantly contribute to the progression of atopic dermatitis and that agents capable of improving brain neural network, stress system, and skin homeostasis may be effective as interventions in the treatment of this condition.

Type I IFNs link skin-associated dysbiotic commensal bacteria to pathogenic inflammation and angiogenesis in rosacea.

Rosacea is a common chronic inflammatory skin disease with a fluctuating course of excessive inflammation and apparent neovascularization. Microbial dysbiosis with a high density of Bacillus oleronius and increased activity of kallikrein 5, which cleaves cathelicidin antimicrobial peptide, are key pathogenic triggers in rosacea. However, how these events are linked to the disease remains unknown. Here, we show that type I IFNs produced by plasmacytoid DCs represent the pivotal link between dysbiosis, the aberrant immune response, and neovascularization. Compared with other commensal bacteria, B. oleronius is highly susceptible and preferentially killed by cathelicidin antimicrobial peptides, leading to enhanced generation of complexes with bacterial DNA. These bacterial DNA complexes but not DNA complexes derived from host cells are required for cathelicidin-induced activation of plasmacytoid DCs and type I IFN production. Moreover, kallikrein 5 cleaves cathelicidin into peptides with heightened DNA binding and type I IFN-inducing capacities. In turn, excessive type I IFN expression drives neoangiogenesis via IL-22 induction and upregulation of the IL-22 receptor on endothelial cells. These findings unravel a potentially novel pathomechanism that directly links hallmarks of rosacea to the killing of dysbiotic commensal bacteria with induction of a pathogenic type I IFN-driven and IL-22-mediated angiogenesis.

Targeting Skin Barrier Function in Atopic Dermatitis

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the general population. Skin barrier dysfunction is the central abnormality leading to AD. The cause of skin barrier dysfunction is complex and rooted in genetic mutations, interactions between the immune pathway activation and epithelial cells, altered host defense mechanisms, as well as environmental influences that cause epithelial cell activation and release of alarmins (such as thymic stromal lymphopoietin) that can activate the type 2 immune pathway, including generation of interleukins 4 and 13, which induces defects in the skin barrier and increased allergic inflammation. These inflammatory pathways are further influenced by environmental factors including the microbiome (especially Staphylococcus aureus), air pollution, stress, and other factors. As such, AD is a syndrome involving multiple phenotypes, all of which have in common skin barrier dysfunction as a key contributing factor. Understanding mechanisms leading to skin barrier dysfunction in AD is pointing to the development of new topical and systemic treatments in AD that helps keep skin borders secure and effectively treat the disease.