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Nocturnal scratching substantially impairs the quality of life in individuals with skin conditions such as atopic dermatitis (AD). Current clinical measurements of scratch rely on patient-reported outcomes (PROs) on itch over the last 24 h. Such measurements lack objectivity and sensitivity. Digital health technologies (DHTs), such as wearable sensors, have been widely used to capture behaviors in clinical and real-world settings. In this work, we develop and validate a machine learning algorithm using wrist-wearing actigraphy that could objectively quantify nocturnal scratching events, therefore facilitating accurate assessment of disease progression, treatment effectiveness, and overall quality of life in AD patients. A total of seven subjects were enrolled in a study to generate data overnight in an inpatient setting. Several machine learning models were developed, and their performance was compared. Results demonstrated that the best-performing model achieved the F1 score of 0.45 on the test set, accompanied by a precision of 0.44 and a recall of 0.46. Upon satisfactory performance with an expanded subject pool, our automatic scratch detection algorithm holds the potential for objectively assessing sleep quality and disease state in AD patients. This advancement promises to inform and refine therapeutic strategies for individuals with AD.

This study investigates the roles of mucosal-associated invariant T (MAIT) cells and Vα7.2 + /CD161 - T cells in skin diseases, focusing on atopic dermatitis. MAIT cells, crucial for bridging innate and adaptive immunity, were analyzed alongside Vα7.2 + /CD161 - T cells in peripheral blood samples from 14 atopic dermatitis patients and 10 healthy controls. Flow cytometry and machine learning algorithms were employed for a comprehensive analysis. The results indicate a significant decrease in MAIT cells and CD69 subsets in atopic dermatitis, coupled with elevated CD38 and polyfunctional MAIT cells producing TNFα and Granzyme B (TNFα + /GzB + ). Vα7.2 + /CD161 - T cells in atopic dermatitis exhibited a decrease in CD8 and IFNγ-producing subsets but an increase in CD38 activated and IL-22-producing subsets. These results highlight the distinctive features of MAIT cells and Vα7.2 + /CD161 - T cells and their different roles in the pathogenesis of atopic dermatitis and provide insights into their potential roles in immune-mediated skin diseases.

Inflammatory skin diseases include a series of disorders characterized by a strong activation of the innate and adaptive immune system in which proinflammatory cytokines play a fundamental role in supporting inflammation. Skin inflammation is a complex process influenced by various factors, including genetic and environmental factors, characterized by the dysfunction of both immune and non-immune cells. Psoriasis (PS) and atopic dermatitis (AD) are the most common chronic inflammatory conditions of the skin whose pathogeneses are very complex and multifactorial. Both diseases are characterized by an immunological dysfunction involving a predominance of Th1 and Th17 cells in PS and of Th2 cells in AD. Suppressor of cytokine signaling (SOCS) proteins are intracellular proteins that control inflammatory responses by regulating various signaling pathways activated by proinflammatory cytokines. SOCS signaling is involved in the regulation and progression of inflammatory responses in skin-resident and non-resident immune cells, and recent data suggest that these negative modulators are dysregulated in inflammatory skin diseases such as PS and AD. This review focuses on the current understanding about the role of SOCS proteins in modulating the activity of inflammatory mediators implicated in the pathogenesis of inflammatory skin diseases such as PS and AD.

Atopic dermatitis (AD) is an inflammatory skin condition that frequently develops before the onset of allergic rhinitis or asthma. More than 10% of children are affected by this serious skin condition, which is painful for the sufferers. Recent research has connected the environment, genetics, the skin barrier, drugs, psychological factors, and the immune system to the onset and severity of AD. The causes and consequences of AD and its cellular and molecular origins are reviewed in this paper. The exploration of interleukins and their influence on the immunological pathway in AD has been facilitated by using relevant biomarkers in clinical trials. This approach enables the identification of novel therapeutic modalities, fostering the potential for targeted translational research within the realm of personalized medicine. This review focuses on AD's pathophysiology and the ever-changing therapeutic landscape. Beyond the plethora of biologic medications in various stages of approval or development, a range of non-biologic targeted therapies, specifically small molecules, have emerged. These include Janus kinase ( JAK ) inhibitors like Baricitinib, Upadacitinib, and Abrocitinib, thus expanding the spectrum of therapeutic options. This review also addresses the latest clinical efficacy data and elucidates the scientific rationale behind each targeted treatment for atopic dermatitis.

Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.

Wound healing is a complex process involving a coordinated series of events aimed at restoring tissue integrity and function. Regulatory B cells (Bregs) are a subset of B lymphocytes that play an essential role in fine-tuning immune responses and maintaining immune homeostasis. Recent studies have suggested that Bregs are important players in cutaneous immunity. This review summarizes the current understanding of the role of Bregs in skin immunity in health and pathology, such as diabetes, psoriasis, systemic sclerosis, cutaneous lupus erythematosus, cutaneous hypersensitivity, pemphigus, and dermatomyositis. We discuss the mechanisms by which Bregs maintain tissue homeostasis in the wound microenvironment through the promotion of angiogenesis, suppression of effector cells, and induction of regulatory immune cells. We also mention the potential clinical applications of Bregs in promoting wound healing, such as the use of adoptive Breg transfer.

In recent years, attention has increasingly focused on various infectious diseases. Although some fatalities are directly attributed to the causative virus, many result from complications and reactive inflammation. Patients with comorbidities are at a higher risk of mortality. Refractory skin conditions such as atopic dermatitis, psoriasis, and epidermolysis bullosa, known for an elevated risk of sepsis, partly owe this to compromised surface barrier function. However, the detailed mechanisms underlying this phenomenon remain elusive. Conversely, although the detrimental effects of a high-fat diet on health, including the onset of metabolic syndrome, are widely recognized, the association between diet and susceptibility to sepsis has not been extensively explored. In this study, we examined the potential causes and pathogenesis of increased sepsis susceptibility in inflammatory skin diseases using a mouse dermatitis model: keratin 14-driven caspase-1 is overexpressed (KCASP1Tg) in mice on a high-fat diet. Our findings reveal that heightened mortality in the dermatitis mouse model is caused by the inflamed immune system due to the chronic inflammatory state of the local skin, and administration of LPS causes a rapid increase in inflammatory cytokine levels in the spleen. Intake of a high-fat diet exacerbates these cytokine levels. Interestingly, we also observed a reduced expression of Toll-like receptor 4 (TLR4) in monocytes from KCASP1Tg mice, potentially predisposing these animals to heightened infection risks and associated complications. Histological analysis showed a clear decrease in T and B cells in the spleen of KCASP1Tg mice fed a high-fat diet. Thickening of the alveolar wall, inflammatory cell infiltration, and alveolar hemorrhage were more prominent in the lungs of KCASP1Tg and KCASP1Tg with fat mice. We postulate that the chronic, non-infectious inflammation induces a negative feedback loop within the inflammatory cascade, and the suppressed expression of TLR4 renders the mice more susceptible to infections. Therefore, it is imperative for individuals with chronic skin inflammation to closely monitor disease progression upon infection and seek timely and appropriate treatment. Additionally, chronic inflammation of adipose tissue, induced by high-fat food intake, combined with dermatitis inflammation, may exacerbate infections, necessitating a review of dietary habits.

Since atopic dermatitis (AD) is a heterogeneous condition, the subtyping of AD is a crucial issue. The classical subtypes of AD are represented by extrinsic and intrinsic subtypes, European-American and Asian subtypes, and adult and pediatric subtypes. While the subtyping of AD was historically conducted based on the phenotype, recent findings on the mechanisms of AD have revealed the importance of the endotype, which can characterize individual patients more accurately. Considering the current development of AD therapies, AD endotyping is a prerequisite for a personalized therapeutic choice. Endotypes of AD can be stratified from different viewpoints, including cytokine expression patterns, allergen properties, epidermal barrier conditions, ceramide variation, the involvement of innate immunity, and serum biomarkers. Among them, the cytokine-based endotype seems to be the most useful one and is categorized into type 2 cytokine (IL-4, IL-13 and IL-31)-high, type 1 cytokine (IFN- γ )-high, and/or type 3 cytokine (IL-22 and IL-17)-high, or mixed subtypes. Recently proposed biomarker endotyping aims at individualized treatment options, although the daily clinical use of endotypes is a future issue. To better understand the endotypes for clinicians, attempts to adjust each of the classical subtypes to endotypes are required. This review will discuss the correspondence of the classical subtypes to the various endotypes that have recently been proposed.

The yes-associated protein (YAP) of the Hippo pathway regulates a variety of target genes involved in cell proliferation, survival, and inflammation. YAP and transcription activator with a PDZ-binding motif (TAZ) proteins act as mediators of the inflammatory response. Still, their role in atopic dermatitis (AD)-particularly, the association with the nuclear factor kappa-B and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways-is not fully understood. In this study, we found that YAP, is upregulated in AD patients and NC/Nga mouse model of AD. In addition, inhibition of YAP significantly reduced epidermal cell proliferation by 58% and mast cell numbers by 51% and attenuated the upregulation of both Th1- and Th2-associated cytokines. Among the JAK-STAT family proteins, the expressions of JAK1 and JAK2 and those of STAT1, STAT2, and STAT3 were also downregulated. These findings may explain the role of YAP in AD and suggest YAP inhibitors as promising therapeutic agents for AD.

Hidradenitis suppurativa is a chronic inflammatory skin disease with limited treatment options. The poorly understood pathogenesis hinders the development of effective treatments; therefore, a pressing need exists to further elucidate the molecular mechanisms in hidradenitis suppurativa. This study investigated the underlying inflammatory pathways and cell types in hidradenitis suppurativa using transcriptomic approaches with RNA sequencing of lesional and non-lesional skin biopsies from hidradenitis suppurativa, which was jointly analyzed with previously published transcriptomic data from atopic dermatitis and psoriasis patients. The differential expression and pathway enrichment analyses demonstrated the activation of multiple inflammatory processes, including the innate and adaptive immune systems, implicated in the hidradenitis suppurativa pathogenesis. In agreement, hidradenitis suppurativa exhibited a unique and heterogeneous cell type signature involving lymphoid and myeloid cells such as B cells and macrophages. Furthermore, hidradenitis suppurativa displayed increased expression of T H 1/2/17 signatures with no predominant T H signatures unlike psoriasis (T H 1/17) and atopic dermatitis (T H 2). In summary, our study provides molecular insights into the pathomechanisms in hidradenitis suppurativa, revealing a strong and widespread immune activation, which may benefit from treatment strategies offering a broad immunomodulation of various key inflammatory pathways. Our data not only corroborate previously reported findings but also enhance our understanding of the immune dysregulation in hidradenitis suppurativa, uncovering novel and potential therapeutic targets.

The skin presents a multifaceted microbiome, a balanced coexistence of bacteria, fungi, and viruses. These resident microorganisms are fundamental in upholding skin health by both countering detrimental pathogens and working in tandem with the skin's immunity. Disruptions in this balance, known as dysbiosis, can lead to disorders like psoriasis and atopic dermatitis. Central to the skin's defense system are mast cells. These are strategically positioned within the skin layers, primed for rapid response to any potential foreign threats. Recent investigations have started to unravel the complex interplay between these mast cells and the diverse entities within the skin's microbiome. This relationship, especially during times of both balance and imbalance, is proving to be more integral to skin health than previously recognized. In this review, we illuminate the latest findings on the ties between mast cells and commensal skin microorganisms, shedding light on their combined effects on skin health and maladies.

Emerging epidemiological evidence links atopic dermatitis (AD) and periodontitis, although the mechanisms remain unclear. Th2-derived cytokines are key in the development of both diseases, and different gingival crevicular fluid (GCF) profiles among healthy and diseased subjects have been previously reported. This case-control study examined the GCF levels of interleukins (IL)-13, IL-31, and thymic stromal lymphopoietin (TSLP) in 29 subjects with moderate-to-severe AD and 33 controls. All subjects underwent comprehensive clinical and oral evaluations, followed by GCF collection. GCF levels of IL-13, IL-31, and TSLP were assessed using a multiplex-bead immunoassay. Demographic and periodontal parameters were similar among groups ( p > 0.05). The GCF levels of IL-31 and TSLP were higher in AD subjects compared to controls ( p < 0.05), whereas no significant differences in the GCF levels of IL-13 were noticed ( p = 0.377). Moderate-to-severe AD was positively associated with the GCF levels of IL-31 and TSLP, whereas severe periodontitis was negatively associated with IL-31 ( p < 0.05). The GCF levels of IL-13 showed no significant associations with either condition ( p = 0.689). There was no significant interaction between AD and periodontitis for IL-31 ( p < 0.869). These results suggest that AD and periodontitis independently influence the GCF levels of IL-31 in opposing ways, whereas AD alone influences the levels of TSLP.

Imbalance of the immune system caused by alterations of the gut microbiome is considered to be a critical factor in the pathogenesis of infant eczema, but the exact role of the gut microbiome in adult atopic dermatitis (AD) patients remains to be clarified. To investigate the differences of the gut microbiome between adult AD patients and healthy individuals, stool samples of 234 adults, containing 104 AD patients and 130 healthy subjects, were collected for 16S rRNA gene amplicon. Altered structure and metabolic dysfunctions of the gut microbiome were identified in adult AD patients. Our results illustrated that the adult AD patients were more likely to have allergies, particularly non-food allergies. In addition, the gut microbiome composition of the AD and normal groups were considerably different. Moreover, Romboutsia and Clostridi-um&#95;sensu&#95;stricto&#95;1 was enriched in the normal group, whereas Blautia , Butyricicoccus , Lachnoclostridium , Eubacterium&#95;hallii&#95;group , Erysi-pelatoclostridium , Megasphaera , Oscillibacter , and Flavonifractor dominated in the AD group. Additionally, purine nucleotide degradation pathways were significantly enriched in the AD group, and the enrichment of proteinogenic amino acid biosynthesis pathways was found in the normal group. This study provides insights into new therapeutic strategies targeting the gut microbiome for AD and evidence for the involvement of the gut-skin axis in AD patients.

Mycoviruses are viruses that selectively infect and multiply in fungal cells. Malassezia is the most abundant fungus on human skin and is associated with a variety of conditions, including atopic eczema, atopic dermatitis, dandruff, folliculitis, pityriasis versicolor, and seborrheic dermatitis. Here, we conducted mycovirome studies on 194 public transcriptomes of Malassezia (2,568,212,042 paired-end reads) screened against all available viral proteins. Transcriptomic data were assembled de novo resulting in 1,170,715 contigs and 2,995,306 open reading frames (ORFs) that were subsequently tracked for potential viral sequences. Eighty-eight virus-associated ORFs were detected in 68 contigs from 28 Sequence Read Archive (SRA) samples. Seventy-five and thirteen ORFs were retrieved from transcriptomes of Malassezia globosa and Malassezia restricta , respectively. Phylogenetic reconstructions revealed three new mycoviruses belonging to the Totivirus genus and named Malassezia globosa-associated-totivirus 1 (MgaTV1); Malassezia restricta-associated-totivirus 1 (MraTV1) and Malassezia restricta-associated-totivirus 2 (MraTV2). These viral candidates extend our understanding of the diversity and taxonomy of mycoviruses as well as their co-evolution with their fungal hosts. These results reflected the unexpected diversity of mycoviruses hidden in public databases. In conclusion, this study sheds light on the discovery of novel mycoviruses and opens the door to study their impact on disease caused by the host fungus Malassezia and globally, their implication in clinical skin disorders.

Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to increase knowledge and develop new targeted therapies. We have recently demonstrated the critical role of NAD + and poly (ADP-ribose) (PAR) metabolism in oxidative stress and skin inflammation. Specifically, we found that hyperactivation of PARP1 in response to DNA damage induced by reactive oxygen species, and fueled by NAMPT-derived NAD + , mediated inflammation through parthanatos cell death in zebrafish and human organotypic 3D skin models of psoriasis. Furthermore, the aberrant induction of NAMPT and PARP activity was observed in the lesional skin of psoriasis patients, supporting the role of these signaling pathways in psoriasis and pointing to NAMPT and PARP1 as potential novel therapeutic targets in treating skin inflammatory disorders. In the present work, we report, for the first time, altered NAD + and PAR metabolism in the skin of AD patients and a strong correlation between NAMPT and PARP1 expression and the lesional status of AD. Furthermore, using a human 3D organotypic skin model of AD, we demonstrate that the pharmacological inhibition of NAMPT and PARP reduces pathology-associated biomarkers. These results help to understand the complexity of AD and reveal new potential treatments for AD patients.

Under physiological conditions, skin mast cells play an important role as guardians that quickly react to stimuli that disturb homeostasis. These cells efficiently support, fight infection, and heal the injured tissue. The substances secreted by mast cells allow for communication inside the body, including the immune, nervous, and blood systems. Pathologically non-cancerous mast cells participate in allergic processes but also may promote the development of autoinflammatory or neoplastic disease. In this article, we review the current literature regarding the role of mast cells in autoinflammatory, allergic, neoplastic skin disease, as well as the importance of these cells in systemic diseases with a pronounced course with skin symptoms.

Allergic diseases are accompanied by a variety of symptoms such as pruritus, coughing, sneezing, and watery eyes, which can result in severe physiological and even psychological impairments. The exact mechanisms of these conditions are not yet completely understood. However, recent studies demonstrated a high relevance of neurotrophins in allergic inflammation, as they induce cytokine release, mediate interaction between immune cells and neurons, and exhibit different expression levels in health and disease. In this review, we aim to give an overview of the current state of knowledge concerning the role of neurotrophins in atopic disorders such as atopic dermatitis, allergic asthma, and allergic rhinitis.

Eosinophilic esophagitis (EoE) is a chronic, Th2-inflammatory disease of the esophagus that can severely affect food intake. Currently, diagnosis and assessing response to treatment of EoE is highly invasive and requires endoscopy with esophageal biopsies. Finding non-invasive and accurate biomarkers is important for improving patient well-being. Unfortunately, EoE is usually accompanied by other atopies, which make it difficult to identify specific biomarkers. Providing an update of circulating EoE biomarkers and concomitant atopies is therefore timely. This review summarizes the current knowledge in EoE blood biomarkers and two of its most common comorbidities, bronchial asthma (BA) and atopic dermatitis (AD), focusing on dysregulated proteins, metabolites, and RNAs. It also revises the current knowledge on extracellular vesicles (EVs) as non-invasive biomarkers for BA and AD, and concludes with the potential use of EVs as biomarkers in EoE.

For patients in rural areas, primary care is often their only access to healthcare services, and skin concerns are among the most common diseases seen in these settings. This study aims to investigate the most common skin conditions, management trends and patterns of referral to dermatology in a rural and underserved community in South Florida. A retrospective chart review was conducted using medical records from the C.L. Brumback Primary Care Clinic in Belle Glade, FL. The most common skin conditions were fungal infections, unspecified dermatitis, pruritus, skin cancer concern, alopecia, and autoimmune skin disorders. The most frequent management strategy was medication prescription followed by specialist referral. Of the 21 percent of patients referred to a specialist, 55 percent of these were to dermatology. The most common diagnoses referred to dermatology were atopic dermatitis and alopecia. Only 20 percent of these patients reported attending their follow-up appointment, and the average distance to referral was 21 miles. Belle Glade is unique in its need for and access to dermatologic care. The lack of access to specialists in rural communities is a public health issue that more studies and outreach initiatives should address., Competing Interests: The authors declare no conflict of interest.

Dysbiosis has been identified in many dermatological conditions (e.g., psoriasis, atopic dermatitis, systemic lupus erythematosus). One of the ways by which the microbiota affect homeostasis is through microbiota-derived molecules (metabolites). There are three main groups of metabolites: short-chain fatty acids (SCFAs), tryptophan metabolites, and amine derivatives including trimethylamine N-oxide (TMAO). Each group has its own uptake and specific receptors through which these metabolites can exert their systemic function. This review provides up-to-date knowledge about the impact that these groups of gut microbiota metabolites may have in dermatological conditions. Special attention is paid to the effect of microbial metabolites on the immune system, including changes in the profile of the immune cells and cytokine disbalance, which are characteristic of several dermatological diseases, especially psoriasis and atopic dermatitis. Targeting the production of microbiota metabolites may serve as a novel therapeutic approach in several immune-mediated dermatological diseases.

Bacteriophages, also known as phages, are viruses that selectively target and infect bacteria. In addition to bacterial dysbiosis, dermatologic conditions such as acne, psoriasis, and atopic dermatitis are characterized by a relative reduction in the abundance of phages and the overgrowth of the corresponding bacteria. Phages often exhibit high specificity for their targeted bacteria, making phage-replacement therapy a promising therapeutic strategy for the control of pathogenic bacteria in dermatologic disease. Novel therapeutic strategies regulating pathogenic bacteria are especially necessary in light of growing antibiotic resistance. In this review, we aimed to review the medical literature assessing phage dysbiosis and therapeutic trials in dermatology. Ultimately, studies have depicted promising results for the treatment of acne, psoriasis, and atopic dermatitis but are limited by low sample sizes and the omission of control groups in some trials. Additional work is necessary to validate the efficacy depicted in proof-of-concept trials and to further determine optimal treatment vehicles, administration mechanisms, and dosing schedules. This review provides the necessary framework for the assessment of phage efficacy in future trials.

Atopic dermatitis (AD) is a common chronic skin disease with pruritus, affecting 5-20% of the population in developed countries. Though its cause varies from genetic polymorphisms to the environmental factors, the T-helper (Th) 2 inflammation is one of the main characteristic pathoses. TNF superfamily ligand A (TL1A) is a recently discovered cytokine, which is released by various immune cells and reported to have an ability to stimulate Th1, Th2, and Th17 responses. Its association was investigated in chronic inflammatory disease, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, its role on AD is unclear. To elucidate the association of TL1A in AD, we measured the serum TL1A levels in AD patients and healthy controls and performed the immunohistochemistry of TL1A. The result showed that the serum TL1A levels were higher in AD patients than healthy controls, and they positively correlated with the serum immunoglobulin E levels, serum Lactate dehydrogenase, and the number of eosinophils in peripheral blood. The immunohistochemistry of TL1A also showed TL1A expression in epithelium of AD samples. Because previous studies indicate TL1A has a certain role as an inflammation enhancer in Th2 and/or Th17 polarized disease, TL1A in AD may also has a role as an inflammation generator.

Next to cow's milk and eggs, plant foods, i.e., legumes, tree nuts and cereal grains, most often sensitise atopic children. Storage proteins constitutes the most relevant protein fraction of plant foods, causing primary sensitisation. They exhibit strong allergenic properties and immunogenicity. Our goal was to analyse sensitisation to 26 plant storage proteins in a group of 76 children aged 0-5 years with chronic symptoms of atopic dermatitis using Allergy Explorer ALEX2 and to discover changes in serum protein-peptide patterns in allergic patients with the use of MALDI-TOF-MS. We reported that 25% of children were allergic to 2S albumins, 19.7% to 7S globulins, 13.2% to 11S globulins and 1.3% to cereal prolamins. The most common allergenic molecules were Ara h 1 (18.4%), Ara h 2 (17.1%), Ara h 6 (15.8%) and Ara h 3 (11.8%) from peanuts, and the mean serum sIgE concentrations in allergic patients were 10.93 kUA/L, 15.353 kUA/L, 15.359 kUA/L and 9.038 kUA/L, respectively. In children allergic to storage proteins compared to the other patients (both allergic and non-allergic), the cell cycle control protein 50A, testis-expressed sequence 13B, DENN domain-containing protein 5A and SKI family transcriptional corepressor 2 were altered. Our results indicate that the IgE-mediated allergy to storage proteins is a huge problem in a group of young, atopic children, and show the potential of proteomic analysis in the prediction of primary sensitisation to plant foods. It is the next crucial step for understanding the molecular consequences of allergy to storage proteins.

The skin is exposed to environmental challenges and contains skin-resident immune cells, including mast cells (MCs) and CD8 T cells that act as sentinels for pathogens and environmental antigens. Human skin MCs and their mediators participate in the maintenance of tissue homeostasis and regulate the recruitment and activity of immune cells involved in the pathogenesis of skin diseases. The cutaneous CD8 T cell compartment is comprised of long-persisting resident memory T cells (T RM ) and migratory or recirculating cells; both populations provide durable site immune surveillance. Several lines of evidence indicate that MC-derived products, such as CCL5 and TNF-α, modulate the migration and function of CD8 T cells. Conversely, activated CD8 T cells induce the upregulation of MC costimulatory molecules. Moreover, the close apposition of MCs and CD8 T cells has been recently identified in the skin of several dermatoses, such as alopecia areata. This review outlines the current knowledge about bidirectional interactions between human MCs and CD8 T cells, analyses the alteration of their communication in the context of three common skin disorders in which these cells have been found altered in number or function-psoriasis, atopic dermatitis, and vitiligo-and discusses the current unanswered questions.

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that imposes significant patient and population burdens. In addition to the cutaneous signs and symptoms, growing evidence suggests that AD is systemic in nature. Certain diseases can possibly co-occur with AD as a result of coincidental exposure to similar environmental factors. However, it is also suspected that they are linked to the pathogenesis of AD through more complex genetic and immunological mechanisms, but these correlations remain less understood. It is of great need to seek explanations for the higher frequency of the number of cardiovascular, autoimmune, neurological, psychiatric, and metabolic disorders that have been observed in epidemiologic investigations among AD patients. Moreover, analysing the immunology of chronic inflammation and its correction, activation, or suppression may prevent the development of a variety of comorbidities. As comorbid diseases in patients diagnosed with AD may potentially go undetected, physicians should be aware of them.

Periostin, identified as a matricellular protein and an ECM protein, plays a central role in non-neoplastic diseases. Periostin and its variants have been considered to be normally involved in the progression of most non-neoplastic diseases, including brain injury, ocular diseases, chronic rhinosinusitis, allergic rhinitis, dental diseases, atopic dermatitis, scleroderma, eosinophilic esophagitis, asthma, cardiovascular diseases, lung diseases, liver diseases, chronic kidney diseases, inflammatory bowel disease, and osteoarthrosis. Periostin interacts with protein receptors and transduces signals primarily through the PI3K/Akt and FAK two channels as well as other pathways to elicit tissue remodeling, fibrosis, inflammation, wound healing, repair, angiogenesis, tissue regeneration, bone formation, barrier, and vascular calcification. This review comprehensively integrates the multiple roles of periostin and its variants in non-neoplastic diseases, proposes the utility of periostin as a biological biomarker, and provides potential drug-developing strategies for targeting periostin.

Skin and gut microbiota play an important role in the pathogenesis of atopic dermatitis (AD). An alteration of the microbiota diversity modulates the development and course of AD, e.g., decreased microbiome diversity correlates with disease severity, particularly in lesional skin of AD. Itch is a hallmark of AD with unsatisfying treatment until now. Recent evidence suggests a possible role of microbiota in altering itch in AD through gut-skin-brain interactions. The microbial metabolites, proinflammatory cytokines, and impaired immune response lead to a modulation of histamine-independent itch, disruption of epidermal barrier, and central sensitization of itch mechanisms. The positive impact of probiotics in alleviating itch in AD supports this hypothesis, which may lead to novel strategies for managing itchy skin in AD patients. This review summarizes the emerging findings on the correlation between an altered microbiota and gut-skin-brain axis in AD, especially in modulating itchy skin.