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International Journal of Biological... 2024Atopic dermatitis (AD) is a common inflammation skin disease that involves dysregulated interplay between immune cells and keratinocytes. Interleukin-38 (IL-38), a...
Atopic dermatitis (AD) is a common inflammation skin disease that involves dysregulated interplay between immune cells and keratinocytes. Interleukin-38 (IL-38), a poorly characterized IL-1 family cytokine, its role and mechanism in the pathogenesis of AD is elusive. Here, we show that IL-38 is mainly secreted by epidermal keratinocytes and highly expressed in the skin and downregulated in AD lesions. We generated IL-38 keratinocyte-specific knockout mice ( ) and induced AD models by 2,4-dinitrofluorobenzene (DNFB). Unexpectedly, after treatment with DNFB, mice were less susceptible to cutaneous inflammation of AD. Moreover, keratinocyte-specific deletion of IL-38 suppressed the migration of Langerhans cells (LCs) into lymph nodes which results in disturbed differentiation of CD4T cells and decreased the infiltration of immune cells into AD lesions. LCs are a type of dendritic cell that reside specifically in the epidermis and regulate immune responses. We developed LC-like cells from mouse bone marrow (BM) and treated with recombined IL-38. The results show that IL-38 depended on IL-36R, activated the phosphorylated expression of IRAK4 and NF-κB P65 and upregulated the expression of CCR7 to promoting the migration of LCs, nevertheless, the upregulation disappeared with the addition of IL-36 receptor antagonist (IL-36RA), IRAK4 or NF-κB P65 inhibitor. Furthermore, after treatment with IRAK4 inhibitors, the experimental AD phenotypes were alleviated and so IRAK4 is considered a promising target for the treatment of inflammatory diseases. Overall, our findings indicated a potential pathway that IL-38 depends on IL-36R, leading to LCs migration to promote AD by upregulating CCR7 via IRAK4/NF-κB and implied the prevention and treatment of AD, supporting potential clinical utilization of IRAK4 inhibitors in AD treatment.
Topics: Animals; Dermatitis, Atopic; Langerhans Cells; Mice; Cell Movement; Mice, Knockout; Interleukin-1; Keratinocytes; Dinitrofluorobenzene; NF-kappa B; Interleukins
PubMed: 38904012
DOI: 10.7150/ijbs.93843 -
Frontiers in Immunology 2024An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the...
An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the features of active stage alopecia areata, with a Severity of Alopecia Tool (SALT) score of 70%. The diagnosis was severe alopecia areata. The patient had a history of atopic dermatitis since infancy, with recurrent episodes of scattered papules and pruritus for 8 years. Initial treatment involved subcutaneous injections of dupilumab 300mg every 2 weeks for 6 months, resulting in a reduction of SALT score to 20% and improvement of atopic dermatitis symptoms. Discontinuation of Dupilumab and initiation of daily oral Baricitinib at a dose of 2mg for a duration of 5 months. According to the SALT score evaluation, the severity of hair loss was less than 10% and there was significant regrowth of hair. No significant adverse reactions were observed during the treatment period.
Topics: Humans; Alopecia Areata; Dermatitis, Atopic; Female; Purines; Child; Azetidines; Pyrazoles; Sulfonamides; Antibodies, Monoclonal, Humanized; Treatment Outcome; Severity of Illness Index; Drug Therapy, Combination
PubMed: 38903518
DOI: 10.3389/fimmu.2024.1395288 -
Frontiers in Immunology 2024Atopic dermatitis (AD) is a common chronic inflammatory skin diseases that seriously affects life quality of the patients. () colonization on the skin plays an...
BACKGROUND
Atopic dermatitis (AD) is a common chronic inflammatory skin diseases that seriously affects life quality of the patients. () colonization on the skin plays an important role in the pathogenesis of AD; however, the mechanism of how it modulates skin immunity to exacerbate AD remains unclear. MicroRNAs are short non-coding RNAs that act as post-transcriptional regulators of genes. They are involved in the pathogenesis of various inflammatory skin diseases.
METHODS
In this study, we established miRNA expression profiles for keratinocytes stimulated with heat-killed (HKSA). The expression of miR-939 in atopic dermatitis patients was analyzed by fluorescence in situ hybridization (FISH). miR-939 mimic was transfected to human primary keratinocyte to investigate its impact on the expression of matrix metalloproteinase genes (MMPs) . Subsequently, miR-939, along with Polyplus transfection reagent, was administered to MC903-induced atopic dermatitis skin to assess its function .
RESULTS
MiR-939 was highly upregulated in HKSA-stimulated keratinocytes and AD lesions. studies revealed that miR-939 increased the expression of matrix metalloproteinase genes, including MMP1, MMP3, and MMP9, as well as the cell adhesion molecule ICAM1 in human primary keratinocytes. studies indicated that miR-939 increased the expression of matrix metalloproteinases to promote the colonization of and exacerbated -induced AD-like skin inflammation.
CONCLUSIONS
Our work reveals miR-939 is an important regulator of skin inflammation in AD that could be used as a potential therapeutic target for AD.
Topics: Dermatitis, Atopic; Humans; MicroRNAs; Staphylococcus aureus; Keratinocytes; Animals; Mice; Matrix Metalloproteinases; Staphylococcal Infections; Female; Male; Disease Models, Animal; Skin; Cells, Cultured
PubMed: 38903509
DOI: 10.3389/fimmu.2024.1354154 -
International Immunopharmacology Jun 2024Shen chan decoction (SCD) as a significant Traditional Chinese medicine (TCM) to treat atopic dermatitis (AD), but its mechanism of action has not been clarified, so we...
Shen chan decoction (SCD) as a significant Traditional Chinese medicine (TCM) to treat atopic dermatitis (AD), but its mechanism of action has not been clarified, so we started the present study, first possible effects of SCD on AD were predicted using network pharmacology. Next, dinitrochlorobenzene was used to establish a mouse model of AD. After successful modelling, the SCD were administered intragastrically to treat the mice. Eventually, the KEGG pathway enrichment analysis indicated that SCD improved AD mainly through effects on inflammation and the gut microbiota. The experimental findings revealed that SCD treatment attenuated AD symptoms and downregulate the characteristic immune factors, namely IL-4, IL-6 and IgE. Moreover, it promoted a balance between Th1/Th2 cells. Furthermore, the itch signaling pathways involving H1R/PAR-2/TRPV1 were inhibited. The 16S rRNA sequencing results indicated that SCD administration influenced the Firmicutes/Bacteroidetes ratio at the phylum level by augmenting the relative proportions of Lactobacillaceae and Muribaculaceae at the family and genus levels, while decreasing the abundances of Lactococcus and Ruminococcus. These findings suggest that internal administration of SCD is an effective therapeutic approach for AD. We suggest that SCD may be an alternative therapy for the treatment of AD.Additionally, it could offer valuable insights into the pathogenesis of AD and the development of innovative therapeutic agents.
PubMed: 38901246
DOI: 10.1016/j.intimp.2024.112479 -
Cureus May 2024A 12-year-old boy with underlying severeand poorly controlled atopic dermatitis (AD) associated with atopic conjunctivitis and rhinitis presented with a right...
A 12-year-old boy with underlying severeand poorly controlled atopic dermatitis (AD) associated with atopic conjunctivitis and rhinitis presented with a right painless blurring of vision for two weeks. On examination, his right eye visual acuity was 1/60,with grade 1 relative afferent pupillary defect (RAPD). Anterior segment examination revealed anterior uveitis with dense posterior subcapsular cataract and hazy fundus view. B-scan ultrasound suggested a shallow total retinal detachment. Intraoperatively, a large retinal dialysis was found. This paper highlights the need for a high index of suspicion of retinal dialysis in a child with underlying AD and the importance of good control of this systemic condition to prevent ocular morbidity.
PubMed: 38899264
DOI: 10.7759/cureus.60660 -
Cureus May 2024Dupilumab, a systemic injectable biologic, can be prescribed to patients with atopic dermatitis who do not respond to topical treatments. Atopy can frequently subside by...
Dupilumab, a systemic injectable biologic, can be prescribed to patients with atopic dermatitis who do not respond to topical treatments. Atopy can frequently subside by blocking inflammatory pathways, such as interleukin-4 (IL-4) and interleukin-13 (IL-13) in the immune system. Dupilumab is generally well-tolerated and mild; the most common adverse reactions listed are arthralgia, back pain, and conjunctivitis, which clears upon cessation or finalization of dupilumab therapy. This case report describes a patient experiencing severe myalgia - a rare adverse effect. The patient's atopic dermatitis was refractory toward topical treatments, but within one month of starting dupilumab, he experienced severe myalgias and muscle spasms, which prompted cessation of dupilumab despite it working well for his atopic dermatitis.
PubMed: 38899260
DOI: 10.7759/cureus.60701 -
Clinical and Translational Allergy Jun 2024Type 2 inflammation has been described as a pathophysiological basis common to some diseases, such as atopic dermatitis (AD), chronic rhinosinusitis with nasal polyps,...
BACKGROUND
Type 2 inflammation has been described as a pathophysiological basis common to some diseases, such as atopic dermatitis (AD), chronic rhinosinusitis with nasal polyps, and asthma (CRSwNP).
OBJECTIVE
The present study used population-based prevalence in Catalonia to analyse the coexistence of type 2 inflammatory diseases in patients primarily diagnosed with the above mentioned conditions.
RESULTS
We found a high degree of coexistence of type 2 inflammatory diseases among these patients, with the prevalence being higher in the severe forms, except for AD. For the severe forms of primary diseases, the proportion of patients with coexisting type 2 inflammatory diseases (severe or non-severe) was 16.2% for AD, 19.8% for asthma, and a striking 62.4% for CRSwNP. This patient population has the highest proportion of coexisting type 2 inflammatory diseases, both severe (48.9%) and non-severe (13.5%).
CONCLUSION
Our findings have significant implications for the management of patients with AD, asthma, and CRSwNP.
PubMed: 38898824
DOI: 10.1002/clt2.12376 -
Acta Dermato-venereologica Jun 2024A Swedish translation of the patient-reported outcome measure for assessing long-term control of atopic dermatitis, Recap of atopic eczema (RECAP), has not been...
A Swedish translation of the patient-reported outcome measure for assessing long-term control of atopic dermatitis, Recap of atopic eczema (RECAP), has not been validated. Cross-cultural translation and multi-centre validation of the translated RECAP questionnaire were therefore performed. Disease severity was assessed using the validated Investigator Global Assessment Scale for atopic dermatitis (vIGA-ADTM). The Swedish RECAP was completed by 208 individuals aged 16 years or older with a median age of 36 years (interquartile range [IQR] 27-48). The participants considered the questionnaire suitable for assessing eczema control. The median RECAP score (range 0-28) was 12 (IQR 5-19). The mean and median vIGA-ADTM scores (range 0-4) were 2 (standard deviation [SD] 2) and 3 (IQR 2-4), respectively. A correlation between RECAP and the vIGA-ADTM was observed (p < 0.001). There was no significant change in scores for participants who answered the questionnaire twice within 14 days. Over time, improved or worsened eczema, as evaluat-ed by vIGA-ADTM, affected RECAP scores significantly (p < 0.001). The study suggests that RECAP can assess AD control in a Swedish clinical setting and shows -acceptable reliability.
Topics: Humans; Dermatitis, Atopic; Adult; Female; Sweden; Male; Middle Aged; Reproducibility of Results; Severity of Illness Index; Patient Reported Outcome Measures; Young Adult; Adolescent; Predictive Value of Tests; Cultural Characteristics; Translating; Surveys and Questionnaires; Time Factors; Cross-Cultural Comparison
PubMed: 38898676
DOI: 10.2340/actadv.v104.38889 -
Frontiers in Immunology 2024Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens....
BACKGROUND
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including ().
OBJECTIVE
To assess whether antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp).
METHODS
To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry.
RESULTS
We identified Esp as the dominant candidate allergen of . Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T cells reacting to Esp were detectable in both AD patients and healthy controls. The T cell response in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients' T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33.
CONCLUSION
The extracellular serine protease Esp of can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that can aggravate AD through the allergenic properties of Esp.
Topics: Humans; Staphylococcus epidermidis; Dermatitis, Atopic; Serine Proteases; Adult; Male; Female; Immunoglobulin E; Bacterial Proteins; Immunoglobulin G; Cytokines; T-Lymphocytes; Allergens; Interleukin-33; Middle Aged
PubMed: 38895118
DOI: 10.3389/fimmu.2024.1352704 -
Sensors (Basel, Switzerland) May 2024Nocturnal scratching substantially impairs the quality of life in individuals with skin conditions such as atopic dermatitis (AD). Current clinical measurements of...
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.
Topics: Humans; Dermatitis, Atopic; Machine Learning; Actigraphy; Wrist; Male; Female; Adult; Algorithms; Pruritus; Wearable Electronic Devices; Quality of Life; Sleep; Middle Aged
PubMed: 38894155
DOI: 10.3390/s24113364