Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

Based on the clinical characteristics of atopic dermatitis( AD) in traditional Chinese medicine( TCM) and Western medicine,the existing animal models were analyzed,and the coincidence degree,advantages and disadvantages between the models and the clinical manifestations of AD were evaluated,so as to provide reference for establishing a rational animal model. After consulting relevant literatures in recent years and summarizing the existing modeling methods,it is found that spontaneous,transgenic/gene knockout models were highly consistent,but with high breeding conditions and expensive prices. The hapten-induced model was low in cost and fast in modeling. It revealed the corresponding mechanism of AD to a certain extent,but did not fully reflect the state of the entire process of AD. The modeling method was guided by Western medicine,but with a lack of pathogenic factors of traditional Chinese medicine,and so has certain limitations in TCM research. Therefore,it is necessary to combine the etiology,pathogenesis and clinical mani-festations of AD with traditional Chinese and Western medicine,so as to improve the coincidence degree between the model and the characteristics of clinical symptoms and lay the foundation for in-depth studies on AD.
Animals ; China ; Dermatitis, Atopic/genetics* ; Drugs, Chinese Herbal ; Eczema ; Medicine ; Medicine, Chinese Traditional

The prevalence and patterns of food allergy are highly variable in different parts of the world. Differences in food allergy epidemiology may be attributed to a complex interplay of genetic, epigenetic, and environmental factors, suggesting that mechanisms of food allergy may differ in various global populations. Genetic polymorphisms, migration, climate, and infant feeding practices all modulate food allergy risk, and possibly also the efficacy of interventions aimed at primary prevention of food allergy development. Approaches to diagnosis, treatment, and prevention of food allergy should thus be tailored carefully to each population's unique genetic and environmental make-up. Future research in the context of food allergy prevention should focus on elucidating factors determining differential responses between populations.
Climate ; Dermatitis, Atopic ; Diagnosis ; Epidemiology ; Epigenomics ; Food Hypersensitivity* ; Genetics ; Humans ; Infant ; Polymorphism, Genetic ; Prevalence ; Primary Prevention

Bamboo salt (BS) is a traditional Korean food, and has been reported to have anti-cancer, anti-inflammatory, and anti-metastatic effects. However, the anti-atopic dermatitis (AD) activity of BS has not been described yet. In the present study, we examined the preventive effect of BS on AD. The effect of oral administration of BS was tested in a 2, 4-dinitrofluorobenzene (DNFB)-induced AD animal model, by histological analysis, enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, caspase-1 assay, and Western blotting analysis. BS administration reduced the total clinical severity and scratching frequencies, compared with the AD group. In the serum of DNFB-induced AD mice, the levels of IgE, histamine, thymic stromal lymphopoietin (TSLP), interleukin (IL)-5, and IL-13 were significantly reduced by BS treatment. BS significantly reduced the protein and mRNA expression of TSLP, IL-6, and tumor necrosis factor-α in the AD skin lesions. BS markedly reduced the infiltration of inflammatory cells. Furthermore, the activation of caspase-1 was reduced by BS in the AD skin lesions. Our results suggested that BS should be considered as a candidate treatment for allergic inflammatory diseases including AD.
Animals ; Caspase 1 ; genetics ; immunology ; Dermatitis, Atopic ; chemically induced ; drug therapy ; genetics ; immunology ; Dinitrofluorobenzene ; adverse effects ; Disease Models, Animal ; Female ; Histamine ; immunology ; Humans ; Immunoglobulin E ; immunology ; Interleukin-13 ; genetics ; immunology ; Interleukin-5 ; genetics ; immunology ; Mice ; Mice, Inbred BALB C ; Sodium Chloride, Dietary ; administration & dosage

Research of the FLG mutation in various ethnic groups revealed non-overlapping mutation patterns. In addition, Japanese and Chinese atopic patients showed somewhat different mutations. These ethnic differences make the research on Korean patients mandatory; however, no systematic research on Korean atopic dermatitis (AD) patients has been performed. This study aims to investigate the genetic polymorphism of FLG in Korean atopic dermatitis patients. The study was made up of three groups including 9 Ichthyosis vulgaris (IV) patients, 50 AD patients and 55 normal controls: the ichthyosis group was incorporated due to the reported association between the FLG mutation and IV. In comparison to other sequencing methods, the overlapping long-range PCR was used. We revealed the genetic polymorphism of filaggrin in Koreans, and at the same time, we discovered nonsense mutations in p.Y1767X and p.K4022X in Korean AD patients. By using FLG sequencing techniques confirmed in this study, new mutations or genetic polymorphisms with ethnic characteristics would be detected and further larger studies of repeat number polymorphisms could be performed.
Adult ; Alleles ; Asian Continental Ancestry Group/*genetics ; Base Sequence ; Codon, Nonsense ; DNA/blood/chemistry/metabolism ; DNA Mutational Analysis ; Dermatitis, Atopic/*genetics ; Female ; Genotype ; Heterozygote ; Humans ; Ichthyosis Vulgaris/genetics ; Intermediate Filament Proteins/*genetics ; Male ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide

Adolescent ; Adult ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; Dermatitis, Atopic ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Infant ; Intermediate Filament Proteins ; genetics ; Male ; Mutation ; Young Adult

Atopic dermatitis (AD) is the most common chronic skin disease of young children and poses a significant global health problem. More than half of children with AD develop asthma and allergies, typically in the first few years of their life. AD is a paradigmatically complex disease with a number of contributing factors, which include genetics, the environment, infection, and skin barrier dysfunction. The diverse clinical phenotypes of AD reflect the genetic and epigenetic background affecting the innate and adaptive immune system, as well as neuro-immunological and environmental factors including microbiologic signals. The gold standard for the management of AD is efficient, ideally proactive, anti-inflammatory treatment combined with strategies aimed at restoring the epidermal barrier. This includes avoidance of trigger factors, skin barrier repair and maintenance, and the use of anti-inflammatory agents. Basic skin care is also considered an important pillar in the management of AD, with functional emollients beginning to appear on the market. In addition, a number of new candidate molecules for the treatment of AD are currently under investigation in clinical trials. Last but not least, treatment compliance remains a key factor for the successful management of AD. Due to its complex clinical phenotype, the future management of AD should be more individualized, addressing personal clinical and genetic/biologic.
Anti-Inflammatory Agents ; Asthma ; Child ; Compliance ; Dermatitis, Atopic* ; Emollients ; Epigenomics ; Genetics ; Humans ; Hypersensitivity ; Immune System ; Phenotype ; Skin ; Skin Care ; Skin Diseases

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease with severe pruritus, and the first step of atopic march since it often precedes asthma or allergic rhinitis. Since its etiology or pathogenesis is very complex and frequently changing, physicians cannot easily understand it in entirety. New insights into the genetics and pathophysiology of AD emphasize the crucial function of the skin barrier as well as abnormal immune response. In this review, the pathogenesis of AD is explained as the combined features of impaired skin barrier and abnormal immune response rather than each independent concept. Understanding the whole pathogenesis of AD may lead to early intervention and prevention of atopic march as well as proper clinical treatment.
Asthma ; Dermatitis, Atopic* ; Early Intervention (Education) ; Genetics ; Hypersensitivity ; Pruritus ; Rhinitis ; Skin ; Skin Diseases

OBJECTIVETo investigate the association of filaggrin gene (FLG) polymorphism with atopic dermatitis (AD) in southern Chinese Han population.

METHODSThe frequencies of the 13 known FLG gene single nucleotide polymorphism(SNPs), including 3321delA, 441delA, 1249insG, E1795X, S3296X, R501X, 2282del4, R2447X, S2889X, 7945delA, 3702delG, Q2417X, R4307X, were detected in a cohort of 50 AD patients and 100 control individuals using polymerase chain reaction (PCR) and DNA sequencing.

RESULTSFLG 3321delA and 441delA were detected in 14 (28%) and 6 (12%) AD patients, respectively. The other 11 SNPs were not detected in the patients. None of the 13 SNPs was detected in the controls.

CONCLUSIONThe results suggested that the FLG gene might be associated with atopic dermatitis susceptibility in southern Chinese Han population.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Child, Preschool ; Dermatitis, Atopic ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Intermediate Filament Proteins ; genetics ; Male ; Polymorphism, Single Nucleotide ; genetics

Th-2-biased immune responses are known to play a key role in the pathogenesis of atopic dermatitis. In particular, the macrophage-derived chemokine CCL22 is directly implicated in Th-2-associated skin inflammatory reactions, and its levels are significantly elevated in serum and are correlated with disease severity in atopic dermatitis. In this study, we tested the development of genetic therapeutic options to treat atopic dermatitis using bacteria expressing miRNA. We constructed a recombinant strain of Salmonella typhimurium expressing CCL22 miRNA (ST-miRCCL22) for the in vivo knockdown of CCL22. The CCL22 gene was downregulated with CCL22 miRNA in activated lymphocytes. In mice with a cutaneous disease similar to atopic dermatitis, interleukin-4 was inhibited and interferon-gamma was induced after treatments with ST-miRCCL22. Furthermore, CCL22 levels were suppressed in the atopic mice treated with ST-miRCCL22. These results suggest that ST-miRCCL22 may be an effective genetic agent for treating atopic dermatitis.
Animals ; Cell Line ; *Chemokine CCL22/genetics ; Cytokines/blood ; Dermatitis, Atopic/pathology ; Disease Models, Animal ; Female ; Gene Expression Regulation/drug effects ; Gene Silencing ; Immunoglobulin E/blood ; Mice ; *MicroRNAs/genetics/pharmacology ; *Organisms, Genetically Modified/genetics ; *Salmonella typhimurium/genetics/metabolism ; Skin/*drug effects/pathology