Seo Hyeong Kim

Individual differences in dupilumab treatment response remain an unmet need. This pilot study aimed to explore transcriptomic changes and candidate molecular signals that may reflect disease activity and treatment response by analyzing gene expression changes in patients with atopic dermatitis (AD) using a minimally invasive microneedle-based skin sampling method (MISSM). Lesional and non-lesional skin samples were collected from six patients with moderate to severe AD before and 16 weeks after dupilumab treatment, and only samples exceeding a predefined complementary RNA (cRNA) yield threshold following pico-scale RNA amplification were analyzed by microarray. Transcriptome profiling identified several genes, including immunoglobulin variable-region and T-cell receptor genes, that showed correlation trends with clinical improvement (change in Eczema Area and Severity Index, ΔEASI) and significant changes after treatment in the responder group. Baseline expression of other immune-related genes, such as chemokines and immunoglobulins, differed between responders and non-responders. As these findings were derived from a small, non-independent cohort, they should be regarded as exploratory signals rather than validated biomarkers. We also demonstrated that MISSM is a feasible platform for multi-layered analysis of molecular changes in AD, supporting its potential utility for longitudinal treatment response monitoring and molecular profiling in chronic inflammatory skin disease.

Sensitive skin is characterized by hypersensitivity to normal stimuli, and objective diagnostic tools and treatments are still limited. Currently, cosmetics for sensitive skin are developed through the exclusion of known irritants rather than investigation into the underlying mechanisms of sensitivity. In this study, we developed an integrated pipeline combining transcriptome analysis via microneedle-based skin sampling (MISSM), bioinformatics, in vitro validation, and clinical assessment to identify sensitive skin-associated inflammatory biomarkers and cosmetic ingredients that regulate them. Candidate biomarkers and matched cosmetic ingredients were identified from transcriptomic data and validated in lactic acid-stimulated HaCaT and human dermal fibroblasts via qRT-PCR. A prototype emulsion was developed and evaluated in a 4-week open-label pilot clinical trial with longitudinal molecular monitoring via MISSM. After lactic acid stimulation, sensitive skin-associated biomarkers (MCOLN1, CYR61, PMAIP1, PTGS2, and HMGB2) were significantly upregulated in both cell types, and cosmetic ingredients that regulate these biomarkers were confirmed in vitro. The emulsion prototype demonstrated hypoallergenicity in a primary irritation test. In the pilot clinical trial, target biomarker expression was significantly reduced in MISSM-derived samples, with improvements in skin hydration, barrier function, redness, and sensory reactivity also observed. This integrated pipeline will enable the discovery of inflammatory biomarker-regulating cosmetic ingredients, with potential applicability to various inflammatory skin conditions.

Skin-resident regulatory T cells (T _reg cells) cells play a critical role in subcutaneous allergen-specific immunotherapy (SIT) for atopic dermatitis (AD). However, a detailed description of the phenotype and origin of skin-resident T _reg cells during SIT is lacking. Therefore, we investigated the role and origin of specific T _reg lineages in SIT with human AD samples and with a mouse model of AD. In the blood of patients with AD who responded to SIT, T _reg cells showed a notable increase in retinoic acid–related orphan receptor γt (RORγt) expression. Moreover, RORγt-expressing T _reg cells expanded in the skin of patients with AD upon SIT. In a mouse model of AD, the absence of RORγt expression in skin T _reg cells led to reduced therapeutic efficacy with SIT. In addition, SIT-induced RORγt ⁺ T _reg cells originated from peripheral tissue rather than from the thymus. Using two-photon microscopy and a parabiosis mouse model, we observed the migration and accumulation of skin-resident RORγt ⁺ T _reg cells in response to the SIT-induced immune response. These findings indicate that SIT induces peripheral RORγt ⁺ T _reg cell expansion, which contributes to the therapeutic efficacy of SIT.

Background: Skin aging can be described as a combination of intrinsic and extrinsic aging. Various parameters for evaluating skin characteristics have been proposed. However, an accurate biomarker for skin aging and the relationship between biomarkers and biomechanical parameters of the skin is yet to be explored.Materials and Methods: This study included 20 subjects by age. Skin aging was measured using non‐invasive devices. Skin tissues were acquired through punch biopsy for immunohistochemistry and qRT‐PCR of skin aging biomarkers, and analyzed correlation both, validated their use.Results: Biomechanical properties of skin aging decreased with age. Among the biomarkers previously reported, we found that the expression of Moesin, TXNDC5, RhoGDI, and RSU1 decreased, while that of Vimentin and FABP5 increased with age. Pearson correlation showed that the expression levels of TXNDC5, RhoGDI, RSU1, and Vimentin were significantly correlated with the results of non‐invasive measurements. In addition, the expression of TXNDC5, RhoGDI, and RSU1 increased, while that of Vimentin decreased, in skin explants upon treatment with one of the anti‐aging compounds, retinoic acid.Conclusion: From this study, we identified practical molecular biomarkers of skin aging, TXNDC5, RhoGDI, RSU1, and Vimentin, which correlated with the skin biomechanical properties of skin aging.