Dermatitis Model Research Articles

P0640 Development and characterization of LQ080, a novel extended half-life bispecific TL1A/IL-23 p19 single domain antibody for the treatment of IBD

Abstract Background Despite the effectiveness of current anti-TL1A treatments, unmet needs remain for effective therapeutics for IBD. Therapies simultaneously neutralizing TL1A and IL-23 might be better choices owing to their synergistic anti-inflammatory effects in the pathogenesis of IBD. Methods TL1A and IL-23 single domain antibodies (sdAbs) were selected from immunized sdAb Phage display libraries. A human whole blood-based assay measuring IFNγ secretion was used to assess functional blockade of TL1A. Mouse splenocytes based assay measuring mouse IL-17 release was used to evaluate functional blockade of IL-23. Dextran Sulfate Sodium (DSS) induced mouse bowel inflammatory model was used to judge the in vivo effect of anti-TL1A antibodies. Synergistic anti-inflammatory effect was evaluated in mouse dermatitis model. Half-life extension was measured via pharmacokinetic analysis in non-human primate (NHP) given a single bolus of LQ080 by subcutaneous administration. Results The TL1A sdAb, which binds to both soluble and membrane-bound TL1A in a pH dependent pattern, potently blocked TL1A/DR3 while leaving the TL1A/DcR3 binding undisturbed and illustrated better IFNγ release in human whole blood induced by TL1A than RVT-3101 and PRA023. In DSS model, the TL1A sdAb also demonstrated better anti-inflammation effect than RVT-3101. The TL1A/IL-23 p19 biparatropic sdAb, LQ080, showed better IFNγ secretion inhibition than RVT-3101 and PRA023, and better inhibition of mouse IL-17 induction than Risankizumab and Guselkumab. Synergistic effects were found using LQ080 in both IFNγ release inhibition in human PBMCs induced by IL-23 and TL1A and in the mouse dermatitis model. The half-life of LQ080 significantly extended of 2-3 folds in non-human primate (NHP) compared to that of RVT-3101. Besides, LQ080 did not form large immune complex in vitro when mixed with TL1A and IL-23. Moreover, LQ080 did not stimulate the release of pro-inflammatory cytokines in the cytokines release assay. Conclusion The TL1A sdAb demonstrated better bioactivity than RVT-3101 and PRA023. LQ080, a TL1A/IL-23 p19 biparatropic sdAb, illustrated synergistic anti-inflammation effect both in vitro and iv vivo for its simultaneous neutralization of TL1A/DR3 and IL-23/IL-23R pathways, which would greatly improve the clinical results of IBD patients. The pH dependent TL1A binding makes LQ080 very different from other anti-TL1A mAbs. LQ080 demonstrated extended half-life in NHP making infrequent dosing possible for IBD treatment. No large immune complex formation when mixed with TL1A and IL-23 would make LQ080 safer when administrated by SC route. Overall, LQ080 is a promising TL1A/IL-23 p19 sdAb for IBD treatment.

P1114 Engineering and Development of a Novel Bispecific Antibody Targeting IL-23 and TL1A

Abstract Background Both IL23 and TL1A are clinically validated targets with genetical linkage to various human autoimmune diseases. Here we engineered and produced HXN-1003, a bispecific antibody (bsAb) simultaneously targeting both IL23 and TL1A, with the aim to further enhance clinical efficacy, and to overcome refractory and resistance associated with single-target based therapies. Methods The binding and blocking efficacy of HXN-1003 for each target were assessed using various in vitro assays, including IL23 reporter and mouse splenocyte activation assays for IL23, and TF-1 apoptosis and DR3-NFκB-Luc reporter assays for TL1A. The synergistic effect of dual targeting was measured by IL22 secretion in mouse splenocytes co-stimulated with IL23 and TL1A. In vivo efficacy was evaluated in hIL23/hTL1A transgenic mice with DSS-induced colitis and IMQ-induced psoriasis models, as well as in SD rats with subcutaneous injections of hTL1A and hIL23 to induce dermatitis. Results HXN-1003 features a tetravalent structure, with the anti-IL23 arm specifically binds to the p19 subunit of IL23, demonstrating superior affinity and blocking activity compared to benchmark Risankizumab. For TL1A, HXN-1003 binds to both the TL1A trimer and monomer with sub-nanomolar affinity, exhibiting similar blocking activity to its parent antibody HXN-1001 and RVT-3101. In the mouse splenocyte activation assay induced by IL23 and TL1A, HXN-1003 showed greater activity than each individual antibody and was equally active to their combination. In animal models, HXN-1003 significantly alleviated symptoms of DSS-induced colitis, and demonstrated superior therapeutic effects in the IMQ-induced psoriasis model compared to the IL23 monoclonal antibody. Additionally, in the dermatitis model induced by hTL1A and hIL23, the bsAb outperformed each individual antibody and their combination. Conclusion HXN-1003 simultaneously blocks IL23 and TL1A, with each arm exhibiting activity comparable to the parent monoclonal antibodies. It has demonstrated synergistic/additive therapeutic effects in both in vitro and in vivo experiments, highlighting its potential to enhance clinical efficacy and benefit autoimmune patients in multiple clinical settings.

Casticin reduces rosacea-related inflammation by inhibiting mast cell activation via Mas-related G protein-coupled receptor X2.

Rosacea is a chronic inflammatory disease characterized by persistent erythema, papules, and pustules, mainly on the skin of the face. Rosacea is difficult to treat; therefore, identifying new treatments is crucial. Mas-related G protein-coupled receptor X2 (MRGPRX2)-mediated mast cell (MC) activation is essential in the pathogenesis of rosacea. Casticin has been shown to exert anti-inflammatory effects; however, it remains unclear whether it can inhibit MRGPRX2 in treating rosacea. This study determined the therapeutic efficacy of casticin against rosacea by inhibiting MRGPRX2-mediated MC activation. A mouse model of LL37-induced rosacea-like dermatitis was employed. The pathological changes were evaluated using hematoxylin and eosin (H&E) staining, and MCs and CD4+ T cells were observed. Inflammatory mediators were analyzed using ELISA. Mouse skin lesions were collected for transcriptomic sequencing. We used an MRGPRX2-mediated MC degranulation model to evaluate the inhibitory effects of casticin in vitro. Molecular docking analysis, molecular dynamics simulations, and surface plasmon resonance evaluated the binding between casticin and MRGPRX2. Casticin attenuated the LL37-induced inflammatory phenotype and reactions in rosacea-like dermatitis. RNA-seq data showed that casticin inhibited MC activation in a mouse model of rosacea. Furthermore, casticin significantly reduced CD4 + T-cell infiltration. Moreover, casticin inhibited MC activation as an MRGPRX2 antagonist in vitro and in vivo by influencing the NF-κB signaling pathway. Our study demonstrated that casticin exhibits therapeutic efficacy against rosacea by inhibiting MC activation via MRGPRX2.

Comparative study of mouse models of atopic dermatitis

Comparative study of mouse models of atopic dermatitis

Beneficial effects of ultrafine bubble shower on a mouse model of atopic dermatitis.

Atopic dermatitis (AD) is a common and relapsing skin disease characterized by skin barrier dysfunction, inflammation, and chronic pruritus. Both cutaneous barrier dysfunction and immune dysregulation are critical etiologies of the pathology of AD. Although various anti-inflammatory pharmacological agents, including cytokine inhibitors and signaling pathway blockers, have been developed recently, keeping the skin clean is of utmost importance in maintaining physiological cutaneous barrier function and avoiding an AD flare. Ultrafine bubbles (UFBs) are less than 1 μm in diameter and usually used to clean medical equipment. A UFB shower is expected to keep skin clean with attention to the temperature and strength of the shower. We examined the effects of a UFB shower on two mouse models of AD: Dermatophagoides farinae body (Dfb)- induced AD in NC/Nga mice and interleukin (IL)-33 transgenic (tg) mice. Each model comprised three groups: UFB shower-treated, normal shower-treated, and untreated. We evaluated the mice using a dermatitis score, scratching counts, histology, and the expression of inflammatory cytokines and skin barrier-related proteins. In the Dfb-induced AD mouse model, clinical features improved markedly in the UFB shower-treated mice compared to other groups. IL-4 and IL-13 levels decreased in the skin of normal and UFB shower-treated mice. In addition, in the skin of UFB shower-treated mice, the expression levels of skin barrier-related proteins were increased compared to normal showertreated mice. However, we found no significant differences in IL33tg mice. These results suggest that UFB shower can recover the skin barrier function and improve skin inflammation, especially in conditions such as extrinsic AD.

Cannabichromene as a Novel Inhibitor of Th2 Cytokine and JAK/STAT Pathway Activation in Atopic Dermatitis Models.

Cannabichromene (CBC) is one of the main cannabinoids found in the cannabis plant, and although less well known than tetrahydrocannabinol (THC) and cannabidiol (CBD), it is gaining attention for its potential therapeutic benefits. To date, CBC's known mechanisms of action include anti-inflammatory, analgesic, antidepressant, antimicrobial, neuroprotective, and anti-acne effects through TRP channel activation and the inhibition of inflammatory pathways, suggesting that it may have therapeutic potential in the treatment of inflammatory skin diseases, such as atopic dermatitis (AD), but its exact mechanism of action remains unclear. Therefore, in this study, we investigated the effects of CBC on Th2 cytokines along with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways involved in AD pathogenesis. We used a 2,4-Dinitrochlorobenzene (DNCB)-induced BALB/c mouse model to topically administer CBC (0.1 mg/kg or 1 mg/kg). The results showed that skin lesion severity, ear thickness, epithelial thickness of dorsal and ear skin, and mast cell infiltration were significantly reduced in the 0.1 mg/kg CBC-treated group compared with the DNCB-treated group (p < 0.001). In addition, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed a significant decrease in the mRNA expression of Th2 cytokines (TSLP, IL-4, IL-13) and inflammatory mediators (IFN-γ, IL-1β, IL-6, IL-17, IL-18, and IL-33) (p < 0.05). Western blot analysis also revealed a significant decrease in JAK1, JAK2, STAT1, STAT2, STAT3, and STAT6 protein expression (p < 0.05). These results suggest that CBC is a promising candidate for the treatment of AD and demonstrates the potential to alleviate AD symptoms by suppressing the Th2 immune response.

T Cells Induce Prolonged Downregulation of Barrier Molecules in a Mouse Model of Allergic Contact Dermatitis.

Dysfunction of the skin barrier is regarded as a key event in the initiation and progression of inflammatory skin diseases. In many cases of allergic contact dermatitis (ACD), epidermal-resident memory CD8+ T (TRM) cells play a central role in the immune response to contact allergens. However, if and how allergen-specific CD8+ TRM cells affect the expression of skin barrier molecules is not known. The expression level of skin barrier molecules was determined by RT-qPCR and immunofluorescence in a mouse model of ACD. The role of CD8+ T cells on the expression of skin barrier molecules was investigated by depletion of CD8+ cells. Human primary keratinocytes were used to assess the direct effect of IFN-γ and contact allergen on their expression of skin barrier molecules. Sensitization with the contact allergen 1-fluoro-2,4-dinitrobenzene (DNFB) resulted in epidermal accumulation of CD8+ TRM cells and prolonged upregulation of Ifng and downregulation of keratin 5 (Krt5) and Krt14 even after complete macroscopic remission of the inflammatory response. Challenge with DNFB lead to an additionally rapid downregulation of Krt5 and Krt14 and the downregulation of several other skin barrier molecules. Depletion of CD8+ cells abolished both the prolonged and rapid downregulation of skin barrier molecules. In keratinocytes, IFN-γ and contact allergen synergistically down-regulated the expression of KRT5 and KRT14. CD8+ TRM cells contribute to a prolonged reduction in the expression of skin barrier molecules, which might exacerbate allergen permeation and the inflammatory response during succeeding exposures of the skin to allergens and antigens.

Agonism of the glutamate receptor GluK2 suppresses dermal mast cell activation and cutaneous inflammation.

Activation of dermal mast cells through the Mas-related G protein-coupled receptor B2 receptor (MrgprB2 in mice and MrgprX2 in humans) is a key component of numerous inflammatory skin diseases, including dermatitis and rosacea. Sensory neurons actively suppress mast cell activation through the regulated release of glutamate, resulting in reduced expression of Mrgprb2 as well as genes associated with proteins found in mast cell granules. To determine whether exogenous glutamate receptor agonism could suppress mast cell function, we determined that mast cells have relatively selective expression of the glutamate receptor ionotropic, kainate 2 (GluK2). A GluK2-specific agonist, SYM2081, effectively inhibited mast cell degranulation in response to MrgprB2 agonism in both murine mast cells and human skin explants in vitro as well as in vivo after both intradermal and topical administration of SYM2081 to mice. Analyses of transcriptomic datasets from SYM2081-treated mast cells using standard differential expression approaches and an interpretable machine learning technique revealed a previously unrecognized cellular program coordinately regulated by GluK2 agonism. GluK2 agonism suppressed the expression of Mrgprb2 and genes associated with mast cell proliferation. Suppression of mast cell proliferation by SYM2081 exposure was confirmed on the basis of reduced Ki-67 expression and BrdU incorporation in vitro and in vivo. Last, pretreatment with SYM2081 reduced skin inflammation in murine models of dermatitis and rosacea. Thus, agonism of GluK2 represents a promising approach to suppress mast cell activation and may prove beneficial as therapy for inflammatory diseases in which mast cell activation is pathogenic.

013 T cells induce prolonged downregulation of barrier molecules in a mouse model of allergic contact dermatitis

013 T cells induce prolonged downregulation of barrier molecules in a mouse model of allergic contact dermatitis

289 Topically applied Hsp90 inhibitor 17-AAG ameliorates skin inflammation in a mouse model of atopic dermatitis

289 Topically applied Hsp90 inhibitor 17-AAG ameliorates skin inflammation in a mouse model of atopic dermatitis

Characterisation and Profiling of Standard Atopic Dermatitis Therapies in a Chronic Dermatitis Murine Model Induced by Oxazolone

ABSTRACTAtopic dermatitis (AD) is a common inflammatory skin disorder characterised by hypersensitivity to allergens, eczematous lesions and pruritus. The aim of this study was to comprehensively characterise a murine model of dermatitis and assess the similarity with the human disease, as well as to profile clinically relevant AD therapies. Four repeated topical administrations of oxazolone in the auricular skin of sensitised mice induced morphological features compatible with AD, including redness and swelling, as well as histological changes typical of spongiotic (eczematous) dermatitis and increased plasmatic IgE. Additionally, key driver Type 2 cytokines involved in the pathophysiology of the disease, IL‐4, IL‐13 and IL − 31, were upregulated in the skin, along with cytokines related to Type 1, 17 and 22 responses, which have been reported to be relevant in the chronic stages of the disease. RNA‐seq studies in OXA model mice samples validate expression changes obtained by q‐PCR and suggest a greater significant similarity with the transcriptomic signature of human AD with respect to psoriasis studies. Oral (cyclosporine, prednisolone and baricitinib) and topical treatments (betamethasone, tacrolimus and crisaborole) were effective inhibiting the induced pathology, as well as modulating the cytokine gene signature of AD. In conclusion, our 4 oxazolone challenges model recapitulates many of the key features of the disease and is responsive to AD standard of care therapies in humans.

294 Staphylococcus hominis is beneficial for skin architecture, barrier and inflammation in an atopic dermatitis model with reconstructed human epidermis

294 Staphylococcus hominis is beneficial for skin architecture, barrier and inflammation in an atopic dermatitis model with reconstructed human epidermis

IL-17A Mediates Depressive-Like Symptoms by Inducing Microglia Activation in Psoriasiform Dermatitis Mice.

Psoriasis is recognized as a systemic disease for its accompanying comorbidities, among which psychological disorders present a high incidence rate and affect patients' life quality. Interleukin (IL)-17A is the central pathological factor in the pathogenesis and development of psoriasis. To clarify if psoriasis-induced systemic IL-17A increase can mediate the neuronal inflammation and result in depressive-like symptoms. Psoriasiform dermatitis model was established by imiquimod (IMQ) application on male BALB/c mice and IL-17A intervention was performed by lateral ventricular catheterization. Skin structural, histopathological characteristics, and behavioral tests were assessed. Serum IL-17A levels were detected by Enzyme-linked immunosorbent assay. mRNA expression of pro-inflammatory factors IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) as well as anti-inflammatory factors IL-4 and IL-10 in the hippocampus and cortex were measured by RT-qPCR. The number of microglia and hippocampal neurons was quantified by immunofluorescent assay. IMQ treatment resulted in significant skin structural and histopathological characters of psoriasiform dermatitis with elevated serum IL-17A levels, obvious depressive-like behaviors, microglia activation with increased IL-1β, IL-6, and TNF-α expression levels in the hippocampus and cortex, and notable inhibition of hippocampal neurogenesis. While, IL-17A neutralization by intracerebroventricular injection of anti-IL-17A antibody can remarkably inhibit microglia activation and decrease the abnormally increased expression levels of IL-1β, IL-6, and TNF-α in the hippocampus and cortex of psoriasiform dermatitis mice, promote hippocampal neurogenesis, thus alleviate the depressive-like behaviors. In the pathological condition of psoriasis, systemic IL-17A elevation can trigger microglia activation, provoke pro-inflammation mediators to release, evoke neuroinflammation, subsequently inhibit hippocampal neurogenesis, and result in depression. IL-17A, as an important pathogenic factor in psoriasis, contributes to its critical role in mediating systemic inflammation and depression comorbidity.

371 N,N-Dimethylglycine sodium salt exerts marked anti-inflammatory effects in various in vitro dermatitis models and activates human epidermal keratinocytes

371 N,N-Dimethylglycine sodium salt exerts marked anti-inflammatory effects in various in vitro dermatitis models and activates human epidermal keratinocytes

026 Characterization of a dermatitis model induced by oxazolone in pig

026 Characterization of a dermatitis model induced by oxazolone in pig

NLRC3 affects the development of psoriasis by modulating the NF-κB signaling pathway mediated inflammatory response through its interaction with TRAF6

ObjectiveThe function and mechanism of NOD-like receptor family CARD-containing 3 (NLRC3) in psoriasis are not yet reported, even though it plays a crucial role in innate and adaptive immunity by inhibiting inflammation. Therefore, this research aims to investigate the role and mechanism of NLRC3 in psoriasis. MethodsHaCaT cells were induced to form a psoriasis cell model using 20 ng/mL IL-1β, 20 ng/mL IL-17A, 20 ng/mL IL-23, 50 ng/mL TNF-α, and 20 ng/mL oncostatin M. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were assessed to determine the proliferation, cell cycle, and apoptosis of HaCaT cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the knockdown efficiency of NLRC3 and TRAF6 interfering RNA in HaCaT cells. Western blot analysis was performed to determine the expression levels of NLRC3, TRAF6, and proteins associated with the NF-κB signaling pathway. A mouse model of psoriasis-like dermatitis was established by evenly applying miquimod cream (62.5 mg/day) to both ears. Hematoxylin-eosin staining was used to measure ear thickness and inflammatory infiltrates in mice. Histological analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL were performed to detect cell proliferation and apoptosis. Interactions between NLRC3 and TRAF6 were predicted using the STRING database (https://cn.string-db.org/). Co-Immunoprecipitation was used to confirm interactions between NLRC3 and TRAF6. Ubiquitination of TRAF6 was assessed by Western blot. ResultsKnockdown of NLRC3 expression promoted cell proliferation and inhibited cell apoptosis in HaCaT cells. In vivo, knockdown of NLRC3 expression significantly increased the infiltration of inflammatory cells and the proliferation of Ki-67 positive cells within mouse ear epidermis, while decreasing the number of apoptotic cells. NLRC3 interacted with TRAF6 and influenced its K63 ubiquitination level. Knockdown of TRAF6 expression resulted in increased cell proliferation and decreased cell apoptosis in HaCaT cells. In vivo, knockdown of TRAF6 expression led to a significant increase in inflammatory cell infiltration and Ki-67 positive cells in mouse ear epidermis, and a decrease in apoptotic cells. Inhibiting the NF-κB signaling pathway alleviated the progression of psoriasis, and interfering with TRAF6 activated the NF-κB signaling axis, contributing to the onset and advancement of psoriasis. ConclusionNLRC3 affects the occurrence of psoriasis by regulating TRAF6 and influencing the NF-κB signaling axis-mediated inflammatory response. This finding offers a theoretical foundation for the treatment of psoriasis.

Regulatory effects of Ishige okamurae extract and Diphlorethohydroxycarmalol on skin barrier function

Ethnopharmacological relevanceThe pharmacological potential of marine organisms remains largely unexplored. Ishige Okamurae, commonly known as Pae, is extensively distributed over Asia. Its antioxidant, antibacterial, antiobesity, and anti-inflammatory properties are also being investigated. Aim of the studyIn most cases of atopic dermatitis, the stratum corneum, the outermost layer of the epidermis, is damaged, causing symptoms such as dryness and hyperproliferation of the epidermis. In particular, the disruption of cell junctions leads to damage of the skin barrier, exacerbating the disease and becoming a target for therapeutic development. Our study aims to investigate of Ishige okamurae extract (IOE) and a major compound derived from it, called Diphlorethohydroxycarmalol (DPHC), can help strengthen the skin barrier in animals with atopic dermatitis induced by 2,4-dinitrochlorobenzene (DNCB). Materials and methodsIn keratinocyte cell lines, HaCaT cells, the cytotoxicity of IOE and DPHC was assessed by MTT analysis. The gene expression of skin barrier factors and tight junctions were determined by real-time PCR in tumor necrosis factor-α/interferon-γ-stimulated HaCaT cells. In addition, JAK/STAT signaling pathway was performed to evaluating the mechanism of drugs by Western blot. Next, we studied the effects of IOE and DPHC on the skin of animals with DNCB-induced atopic dermatitis. We measured the expression of genes related of the skin barrier and tight junctions in their ear tissue. ResultsAs a result, IOE and DPHC confirmed that the expression of skin barrier proteins (thymic stromal lymphopoietin, filaggrin, loricrin, and involucrin) was improved in the DNCB-induced atopic dermatitis model and HaCaT cells. In addition, the expression of tight junction-related proteins (claudin, occludin, and tight junction protein-1) were improved. ConclusionIOE and DPHC ameliorated the atopic dermatitis lesions through alleviating the pro-inflammatory responses and tight junction protein destruction. Our results suggest that IOE and DPHC could be promising candidates for enhancing skin barrier function.

The Influence of Skin Microbial Ecology on γδ T Cell Immune Pathways in Allergic Dermatitis Models in Mice.

Atopic dermatitis (AD) is a complex disease influenced by alterations in the skin microbiome and immune dysregulation. Despite the recognized role of these factors, the specific pathways by which distinct microbial populations affect skin immunity remain insufficiently understood. On a molecular level, the pathogenesis of AD involves critical cytokines such as IL-4, IL-17, interferon-γ (IFN-γ), and IL-10, which contribute to the imbalance in T helper (Th) cell responses. Importantly, gamma-delta (γδ) T cells, which produce these cytokines and infiltrate affected epithelial cells in AD, have been underexplored. This study seeks to alleviate AD symptoms in mice by adjusting both peripheral and local immune environments through the transplantation of skin microbiota. By employing 16S rRNA sequencing, we characterized the skin microbiome of the mouse model. Our results demonstrate that microbiota intervention significantly reduces skin thickening and serum IgE levels in DNFB-induced AD mice. Additionally, changes in skin microbiota modulated immune cell dynamics, restoring the Th1/Th2 balance and leading to clinical improvement. These findings highlight the critical role of skin microbiota in shaping immune responses, positioning microbiota-based therapies as a potential treatment for AD.

Immune response to topical sodium lauryl sulfate differs from classical irritant and allergic contact dermatitis.

Sodium lauryl sulfate (SLS) is used as a control irritant in patch testing for allergic contact dermatitis (ACD). However, up to 20% of those tested react to SLS, whereby the pathophysiological basis of this reaction is still unclear. To mimic patch test reactions, we repeatedly applied SLS to the skin of wild-type mice. Reactions were compared with those in a classical ACD model induced by oxazolone and an irritant contact dermatitis (ICD) model induced by croton oil. Skin inflammation was assessed with ear thickness measurements, immunohistochemistry, qRT-PCR, and flow cytometry. Topical SLS treatment was further investigated in Flg/Hrnr-/-, Myd88/Tlr3-/-, and Rag1-/- mouse models. All three compounds caused ear swelling with different courses. Oxazolone treatment, compared with the ICD model, resulted in a greater influx of immune cells (CD4+, MHCII+, CD11b+). Similarly, SLS did not induce immune cell infiltration or expression of selected inflammatory and regulatory cytokines. SLS induced the most pronounced keratinocyte proliferation. Compared with wild-type mice, topical SLS application did not increase ear swelling in skin barrier deficient Flg/Hrnr-/- mice, but led to significantly delayed swelling in mice with defects in innate or adaptive immune functions (Myd88/Tlr3-/-, Rag1-/-). SLS-induced contact dermatitis differed from classical ACD and ICD, as it elicited less pronounced immune alterations. Skin barrier impairment does not affect SLS-induced contact dermatitis, whereas both innate and adaptive components are involved in SLS skin reactions.

A Multi-model Deep Learning Architecture for Diagnosing Multi-class Skin Diseases.

Skin diseases are a significant global public health concern, affecting 21-85% of the world's population, particularly those in low- and middle-income countries. Accurate and timely diagnosis is crucial for effective treatment and improved patient outcomes. This study introduces a novel deep-learning multi-model architecture designed for high-precision skin disease diagnosis. The system employs a five-category Xception model to classify skin lesions into five classes: Atopic Dermatitis, Acne and Rosacea, Skin Cancer, Bullous, and Others. Trained on 25,010 images, the model achieved 95% accuracy and an AUROC of 99.4%. To further enhance accuracy, transfer learning was applied, resulting in specialized models for each class, with strong performance across 40 skin conditions. Specifically, the Acne and Rosacea model achieved an accuracy of 90.0%, with a precision of 90.7%, recall of 90.1%, f1-score of 90.2%, and an AUROC of 99.0%. The Skin Cancer model demonstrated 94.0% accuracy, 94.8% precision, 94.2% recall, 94.1% f1-score, and a 99.5% AUROC. The Atopic Dermatitis model reported 91.8% accuracy, 92.2% precision, 91.8% recall, 91.9% f1-score, and a 98.8% AUROC. Finally, the Bullous model showed 90.0% accuracy, 90.6% precision, 90.0% recall, 90.0% f1-score, and a 98.9% AUROC. This approach surpasses previous studies, offering a more comprehensive diagnostic tool for skin diseases. To facilitate result reproducibility, the training and testing codes for the models utilized in this study are accessible via the GitHub repository ( https://github.com/SaraEl-Metwally/A-Multi-Model-Deep-Learning-for-Diagnosing-Skin-Diseases ).