-
EMBO Molecular Medicine Jun 2024Thymic stromal lymphopoietin (TSLP) is a key player in atopic diseases, which has sparked great interest in therapeutically targeting TSLP. Yet, no small-molecule TSLP...
Thymic stromal lymphopoietin (TSLP) is a key player in atopic diseases, which has sparked great interest in therapeutically targeting TSLP. Yet, no small-molecule TSLP inhibitors exist due to the challenges of disrupting the protein-protein interaction between TSLP and its receptor. Here, we report the development of small-molecule TSLP receptor inhibitors using virtual screening and docking of >1,000,000 compounds followed by iterative chemical synthesis. BP79 emerged as our lead compound that effectively abrogates TSLP-triggered cytokines at low micromolar concentrations. For in-depth analysis, we developed a human atopic disease drug discovery platform using multi-organ chips. Here, topical application of BP79 onto atopic skin models that were co-cultivated with lung models and Th2 cells effectively suppressed immune cell infiltration and IL-13, IL-4, TSLP, and periostin secretion, while upregulating skin barrier proteins. RNA-Seq analysis corroborate these findings and indicate protective downstream effects on the lungs. To the best of our knowledge, this represents the first report of a potent putative small molecule TSLPR inhibitor which has the potential to expand the therapeutic and preventive options in atopic diseases.
PubMed: 38877290
DOI: 10.1038/s44321-024-00085-3 -
Frontiers in Pharmacology 2024In China, plants are widely used to reduce atopic dermatitis and inflammation-related diseases, but their protective mechanisms remain unclear. This study investigated...
In China, plants are widely used to reduce atopic dermatitis and inflammation-related diseases, but their protective mechanisms remain unclear. This study investigated the anti-allergic dermatitis, anti-oxidation and anti-inflammation effect and underlying mechanism of five species, including , var. , , , and . . A total of about 110 chemical compositions were detected from five teas extracts. The level of mast cell infiltration in the model mice skin was determined by HE (Hematoxylin and eosin) staining and toluidine blue staining, and the level of interleukin-1 (IL-1β) and nerve growth factor was detected by immunohistochemistry. The five Camellia tea leaf extracts have histamine-induced allergic dermatitis. Lipopolysaccharide (Lipopolysaccharide)-induced murine macrophage RAW264.7 inflammation model was found to secrete NF-κB factor, as shown by immunofluorescence, and reactive oxygen species secretion and related cytokine levels were detected. The results suggested that Camellia's five tea extracts had the ability to resist cellular oxidative stress. In addition, the results of cell inflammatory cytokines including fibronectin (FN) and interleukin-6 (IL-6) suggested that the five tea extracts of had anti-inflammatory effects. Therefore, it is suggested that five teas may possess inhibitory properties against allergic reactions, oxidative stress, and inflammation, and may prove beneficial in the treatment of allergies.
PubMed: 38873420
DOI: 10.3389/fphar.2024.1296190 -
PloS One 2024Air pollution causes and exacerbates allergic diseases including asthma, allergic rhinitis, and atopic dermatitis. Precise prediction of the number of patients afflicted...
Air pollution causes and exacerbates allergic diseases including asthma, allergic rhinitis, and atopic dermatitis. Precise prediction of the number of patients afflicted with these diseases and analysis of the environmental conditions that contribute to disease outbreaks play crucial roles in the effective management of hospital services. Therefore, this study aims to predict the daily number of patients with these allergic diseases and determine the impact of particulate matter (PM10) on each disease. To analyze the spatiotemporal correlations between allergic diseases (asthma, atopic dermatitis, and allergic rhinitis) and PM10 concentrations, we propose a multi-variable spatiotemporal graph convolutional network (MST-GCN)-based disease prediction model. Data on the number of patients were collected from the National Health Insurance Service from January 2013 to December 2017, and the PM10 data were collected from Airkorea during the same period. As a result, the proposed disease prediction model showed higher performance (R2 0.87) than the other deep-learning baseline methods. The synergic effect of spatial and temporal analyses improved the prediction performance of the number of patients. The prediction accuracies for allergic rhinitis, asthma, and atopic dermatitis achieved R2 scores of 0.96, 0.92, and 0.86, respectively. In the ablation study of environmental factors, PM10 improved the prediction accuracy by 10.13%, based on the R2 score.
Topics: Humans; Particulate Matter; Asthma; Rhinitis, Allergic; Dermatitis, Atopic; Air Pollution; Spatio-Temporal Analysis; Air Pollutants; Neural Networks, Computer; Hypersensitivity
PubMed: 38870112
DOI: 10.1371/journal.pone.0304106 -
Frontiers in Immunology 2024Chronic inflammatory skin diseases are multifactorial diseases that combine genetic predisposition, environmental triggers, and metabolic disturbances associated with... (Review)
Review
Chronic inflammatory skin diseases are multifactorial diseases that combine genetic predisposition, environmental triggers, and metabolic disturbances associated with abnormal immune responses. From an immunological perspective, the better understanding of their physiopathology has demonstrated a large complex network of immune cell subsets and related cytokines that interact with both epidermal and dermal cells. For example, in type-1-associated diseases such as alopecia areata, vitiligo, and localized scleroderma, recent evidence suggests the presence of a type-2 inflammation that is well known in atopic dermatitis. Whether this type-2 immune response has a protective or detrimental impact on the development and chronicity of these diseases remains to be fully elucidated, highlighting the need to better understand its involvement for the management of patients. This mini-review explores recent insights regarding the potential role of type-2-related immunity in alopecia areata, vitiligo, and localized scleroderma.
Topics: Humans; Vitiligo; Animals; Alopecia Areata; Th2 Cells; Cytokines; Dermatitis, Atopic; Scleroderma, Localized; Inflammation; Skin
PubMed: 38868763
DOI: 10.3389/fimmu.2024.1405215 -
Frontiers in Medicine 2024
PubMed: 38868748
DOI: 10.3389/fmed.2024.1431191 -
BMC Ophthalmology Jun 2024The prevalence of rejection is 10-30% in penetrating keratoplasty (PKP) case, and the rate is higher in cases of high-risk patients. Although using topical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The prevalence of rejection is 10-30% in penetrating keratoplasty (PKP) case, and the rate is higher in cases of high-risk patients. Although using topical corticosteroids is a standard method for management the rejection of post-PKP patients, it may not be sufficiently potent in high-risk patients. Topical administration of tacrolimus (TAC) may be effective in suppression rejection after corneal transplantation. This study aimed to investigate the efficacy and safety of topical TAC in high-risk PKP patients in Japan.
METHODS
This study was a single centre, single-blinded, randomized controlled trial. Patients with a history of PKP, graft rejection, atopic dermatitis, or deep corneal neovascularisation who underwent PKP were enrolled. They were randomly assigned to receive 0.1% TAC ophthalmic suspension or artificial tear (AT) up to week 52 after surgery. All participants received 0.1% betamethasone up to week 13 after surgery then they received 0.1% fluorometholone up to week 52. The incidence of immunological rejection during the observation period was the main outcome measure in this study.
RESULTS
Thirty patients were enrolled in this study, and 12 eyes in the TAC group and 13 eyes in the AT group completed the study, respectively. Five out of 30 patients discontinued participation after providing informed consent. No serious adverse effects were developed in patients who received 0.1% TAC ophthalmic suspension. No rejection episodes occurred in the TAC group, while one eye in the AT group had rejection. Graft clarity, best spectacle-corrected visual acuity, intraocular pressure, and corneal endothelial cell density were not significantly different between the TAC and AT groups.
CONCLUSION
Our results demonstrated that good tolerability of 0.1% TAC ophthalmic suspension. However, we failed to demonstrate its efficacy in preventing immunological rejection in high-risk patients undergoing PKP.
TRIAL REGISTRATION
This study was first registered in the University Hospital Medical Information Network (UMIN000029669, Date of registration: November 1, 2017). With the enforcement of the Clinical Trial Act in Japan, the study re-registered in the Japan Registry of Clinical Trials (jRCTs031180342, Date of registration: March 18, 2019).
Topics: Humans; Tacrolimus; Female; Male; Immunosuppressive Agents; Middle Aged; Graft Rejection; Aged; Ophthalmic Solutions; Keratoplasty, Penetrating; Single-Blind Method; Administration, Topical; Visual Acuity; Adult
PubMed: 38867175
DOI: 10.1186/s12886-024-03506-6 -
Frontiers in Immunology 2024The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between...
BACKGROUND
The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between regulatory T cell (Treg) immune traits and ADs complicated by NHL remains debated.
METHODS
Aggregate data for 84 Treg-related immune traits were downloaded from the Genome-Wide Association Study (GWAS) catalog, and GWAS data for diffuse large B-cell lymphoma (DLBCL; n=315243), follicular lymphoma (FL; n=325831), sjögren's syndrome (SS; n=402090), rheumatoid arthritis (RA; n=276465), dermatopolymyositis (DM; n=311640), psoriasis (n=407876), atopic dermatitis (AD; n=382254), ulcerative colitis (UC; n=411317), crohn's disease(CD; n=411973) and systemic lupus erythematosus (SLE; n=307587) were downloaded from the FinnGen database. The inverse variance weighting (IVW) method was mainly used to infer any causal association between Treg-related immune traits and DLBCL, FL, SS, DM, RA, Psoriasis, AD, UC, CD and SLE, supplemented by MR-Egger, weighted median, simple mode, and weighted mode. Moreover, we performed sensitivity analyses to assess the validity of the causal relationships.
RESULTS
There was a potential genetic predisposition association identified between CD39+ CD8br AC, CD39+ CD8br % T cell, and the risk of DLBCL (OR=1.51, p<0.001; OR=1.25, p=0.001) (adjusted FDR<0.1). Genetic prediction revealed potential associations between CD25++ CD8br AC, CD28- CD25++ CD8br % T cell, CD39+ CD8br % CD8br, and the risk of FL (OR=1.13, p=0.022; OR=1.28, p=0.042; OR=0.90, p=0.016) (adjusted FDR>0.1). Furthermore, SLE and CD exhibited a genetically predicted potential association with the CD39+ CD8+ Tregs subset. SS and DM were possibly associated with an increase in the quantity of the CD4+ Tregs subset; RA may have reduced the quantity of the CD39+ CD8+ Tregs subset, although no causal relationship was identified. Sensitivity analyses supported the robustness of our findings.
CONCLUSIONS
There existed a genetically predicted potential association between the CD39+ CD8+ Tregs subset and the risk of DLBCL, while SLE and CD were genetically predicted to be potentially associated with the CD39+ CD8+ Tregs subset. The CD39+ CD8+ Tregs subset potentially aided in the clinical diagnosis and treatment of SLE or CD complicated by DLBCL.
Topics: Humans; T-Lymphocytes, Regulatory; Genome-Wide Association Study; Mendelian Randomization Analysis; Risk Factors; Autoimmune Diseases; Lymphoma, Non-Hodgkin; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38863695
DOI: 10.3389/fimmu.2024.1374938 -
Biomedicine & Pharmacotherapy =... Jul 2024Atopic dermatitis (AD) is a globally increasing chronic inflammatory skin disease with limited and potentially side-effect-prone treatment options. Monotropein is the...
Atopic dermatitis (AD) is a globally increasing chronic inflammatory skin disease with limited and potentially side-effect-prone treatment options. Monotropein is the predominant iridoid glycoside in Morinda officinalis How roots, which has previously shown promise in alleviating AD symptoms. This study aimed to systematically investigate the pharmacological effects of monotropein on AD using a 2, 4-dinitrochlorobenzene (DNCB)/Dermatophagoides farinae extract (DFE)-induced AD mice and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated keratinocytes. Oral administration of monotropein demonstrated a significant reduction in AD phenotypes, including scaling, erythema, and increased skin thickness in AD-induced mice. Histological analysis revealed a marked decrease in immune cell infiltration in skin lesions. Additionally, monotropein effectively downregulated inflammatory markers, encompassing pro-inflammatory cytokines, T helper (Th)1 and Th2 cytokines, and pro-inflammatory chemokines in skin tissues. Notably, monotropein also led to a considerable decrease in serum immunoglobulin (Ig)E and IgG2a levels. At a mechanistic level, monotropein exerted its anti-inflammatory effects by suppressing the phosphorylation of Janus kinase / signal transducer and activator of transcription proteins in both skin tissues of AD-induced mice and TNF-α/IFN-γ-stimulated keratinocytes. In conclusion, monotropein exhibited a pronounced alleviation of AD symptoms in the experimental models used. These findings underscore the potential application of monotropein as a therapeutic agent in the context of AD, providing a scientific basis for further exploration and development.
Topics: Animals; Dermatitis, Atopic; Signal Transduction; Mice; Janus Kinases; Skin; Keratinocytes; Cytokines; Mice, Inbred BALB C; STAT Transcription Factors; Humans; Dinitrochlorobenzene; Anti-Inflammatory Agents; Female; Disease Models, Animal; Inflammation; Immunoglobulin E; Dermatophagoides farinae; Iridoids
PubMed: 38861857
DOI: 10.1016/j.biopha.2024.116911 -
Acta Dermato-venereologica Jun 2024Atopic dermatitis is a prevalent skin condition that affects up to 17% of adult population. It can lead to itching, pain, and other symptoms such as sleep disturbance,...
Atopic dermatitis is a prevalent skin condition that affects up to 17% of adult population. It can lead to itching, pain, and other symptoms such as sleep disturbance, anxiety, and depression. Due to its high prevalence and limiting symptoms, atopic dermatitis often has a great impact on patients' quality of life but there is scarce information regarding how atopic dermatitis affects women's sexual health and reproductive desires. The purpose of this article was to assess the impact of atopic dermatitis on sexual function and reproductive wishes in women. A cross-sectional study was conducted from February to March 2022. A total of 102 women with atopic dermatitis were recruited through online questionnaires sent through the Spanish Atopic Dermatitis Association; 68.6% of the patients acknowledged impairment in sexual function, especially those with more severe disease and those with genital and gluteal involvement. In addition, 51% of the women considered that atopic dermatitis may have an influence on their gestational desire, particularly those with gluteal involvement. In conclusion, atopic dermatitis has a great impact on sexual function and reproductive desires in women.
Topics: Humans; Female; Dermatitis, Atopic; Adult; Cross-Sectional Studies; Quality of Life; Sexual Dysfunction, Physiological; Middle Aged; Young Adult; Sexual Dysfunctions, Psychological; Surveys and Questionnaires; Sexual Behavior; Libido; Severity of Illness Index; Sexual Health
PubMed: 38860625
DOI: 10.2340/actadv.v104.35107 -
Acta Dermato-venereologica Jun 2024Patients with atopic dermatitis (AD) are more likely than healthy individuals to harbour Staphylococcus aureus on their skin. Superantigens (SAgs) produced by specific...
Patients with atopic dermatitis (AD) are more likely than healthy individuals to harbour Staphylococcus aureus on their skin. Superantigens (SAgs) produced by specific S. aureus strains may contribute to AD-associated skin inflammation. The present study compared the prevalence and types of SAg-encoding genes between S. aureus isolated from patients with AD and from controls, and within the AD group between isolates from different sampling sites (lesional skin, non-lesional skin, and nares). This retrospective case-control study extracted data from 2 previous studies that examined S. aureus using whole-genome sequencing. The 138 S. aureus isolates obtained from 71 AD patients contained 349 SAg-encoding genes; 22 (6.3%) were found in isolates from nares (0.4 ± 0.6 genes per isolate), 99 (28.4%) in isolates from non-lesional skin (3.7 ± 3.9), and 228 (65.3%) in isolates from lesional skin (4.2 ± 4.5). S. aureus (n = 101) from the control group contained 594 SAg-encoding genes (5.9 ± 4.2). Of the S. aureus isolated from lesional AD skin, 69% carried at least 1 gene encoding SAg compared with 33% of AD nasal isolates. SAg could be a factor in the pathogenesis of a subset of AD patients.
Topics: Humans; Dermatitis, Atopic; Superantigens; Staphylococcus aureus; Retrospective Studies; Skin; Male; Female; Case-Control Studies; Adult; Staphylococcal Skin Infections; Middle Aged; Young Adult
PubMed: 38860624
DOI: 10.2340/actadv.v104.34882