Psoriasis is a chronic inflammatory skin disease with a Th17-skewed immune phenotype. Although it has been generally accepted that regulatory T cells (Tregs) in lesional psoriatic skin have functional impairment due to the local inflammatory microenvironment, the molecular properties of skin-homing psoriatic Tregs have not been well explored. We designed an extensive 39 marker mass cytometry (CyTOF) panel to deeply profile the immune landscape of skin-homing Tregs from 31 people with psoriasis stratified by psoriasis area severity index score as mild (n = 15) to moderate-severe (n = 16) and 32 healthy controls. We further validated the findings with an in-vitro chemokine-mediated Treg migration assay, immunofluorescent imaging of normal and psoriatic lesional skin and analysed public single-cell RNA-sequencing datasets to expand upon our findings into the local tissue microenvironments. We discovered an overall decrease in CLAhi Tregs and specifically, CLAhiCCR5+ Tregs in psoriasis. Functional markers CD39 and FoxP3 were elevated in psoriatic Tregs. However, CCR7 expression was significantly increased while CCR4 and CLA expression was reduced in psoriatic Tregs and CLAhi Tregs, which was associated with disease severity. Moreover, psoriatic Tregs revealed increased migratory capacity towards CCR7's ligands, CCL19/CCL21. Interrogation of public single-cell RNA sequencing data confirmed reduced expression of skin-trafficking markers in lesional-skin Tregs compared to non-lesioned skin, further substantiated by immunofluorescent staining. Psoriatic circulating Tregs showed an impaired skin-trafficking phenotype thus leading to insufficient suppression of ongoing inflammation in the lesional skin, expanding upon our current understanding of the impairment of Treg-mediated immunosuppression in psoriasis. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and Information and Communications Technology (2020R1C1C1014513, 2021R1A4A5032185, 2020R1F1A1073692); and the new faculty research seed money grant of Yonsei University College of Medicine for 2021 (2021-32-0033).

Introduction: The stratum corneum (SC) is a skin barrier that consists of corneocytes, intercellular lipids, and corneodesmosomes. Ceramides are composed of sphingoid bases linked with various types of fatty acids (FAs), and they are an essential constituent of SC intercellular lipids. Among their subtypes, ceramide NP with a phytosphingosine base is especially important. Most of the previous studies on barrier recovery have focused on a specific ceramide with a single chain FA, not with diverse chain lengths. Skin barrier function is impaired by various factors, including topical corticosteroid. Objective: We evaluated whether a lipid mixture enriched by ceramide NP with FAs of diverse chain lengths (CER [NP]*) can restore the skin barrier function impaired by topical corticosteroid. Methods: Twenty-seven healthy adult male volunteers were recruited. Topical corticosteroid was applied on both volar forearms of volunteers. Then, the test cream containing a lipid mixture with CER (NP)* was applied on the left forearm, and a vehicle cream without a lipid mixture was applied on the right forearm of each subject. The functional parameters of the skin barrier were compared before and after the treatment. Epidermal differentiation markers, hyaluronic acid synthase 3 (HAS3), cytokine levels, and the lipid profiles in the SC were analyzed. Results: The functional parameters of the skin barrier, such as barrier recovery rate, SC integrity, and SC hydration were significantly improved in the test cream-applied site compared to the vehicle cream-applied sites. Filaggrin and HAS3 levels were significantly higher in the sites applied with the test cream. Interleukin (IL)-1α levels were also significantly increased in these sites. IL-2, IL-6, IL-10, and IL-13 levels were significantly decreased in the test cream-applied sites. Lipid analyses showed that C18, C20, and total ceramide NP levels significantly increased in the sites where the test cream was applied. Also, C16, C18, C20, C24, and total ceramide NP levels were significantly elevated in the test cream-applied sites after acute barrier disruption. Conclusion: Our results demonstrate that a lipid mixture enriched by CER (NP)* could recover the barrier function impaired by topical corticosteroid.

Background: Various comorbid diseases have been reported in patients with lichen planopilaris (LPP); however, data regarding the risks of incident diseases and mortality are lacking. Objectives: To investigate the risks of incident diseases and mortality associated with LPP. Methods: This was a retrospective nationwide population-based study, using data from the National Health Insurance Service Database of Korea from 2002 to 2019. Patients aged ≥ 18 years with three or more documented medical visits for LPP were included. The adjusted hazard ratios (aHRs) for incident disease outcomes and mortality were compared with 1 : 20 age-, sex-, insurance type- and income-level-matched controls. Results: In total, 2026 patients with LPP and 40 520 controls were analysed. The risks of incident systemic lupus erythematosus [aHR 1.91, 95% confidence interval (CI) 1.21–3.03], psoriasis (aHR 3.42, 95% CI 2.83–4.14), rheumatoid arthritis (aHR 1.39, 95% CI 1.19–1.63), lichen planus (aHR, 10.07, 95% CI 7.17–14.15), atopic dermatitis (aHR 2.15, 95% CI 1.90–2.44), allergic rhinitis (aHR 1.29, 95% CI 1.13–1.49), thyroid diseases (hyperthyroidism: aHR 1.42, 95% CI 1.14–1.77, hypothyroidism aHR 1.19 95% CI 1.01–1.41, and thyroiditis: aHR, 1.35, 95% CI 1.08–1.69), nonmelanoma skin cancer (aHR 2.33, 95% CI 1.00–5.44) and vitamin D deficiency (aHR 1.23, 95% CI 1.03–1.47) were higher in patients with LPP. Patients with LPP had a higher mortality rate than controls (aHR 1.30, 95% CI 1.04–1.61), although the risk was not significant after adjusting for comorbidities (aHR 1.08, 95% CI 0.87–1.34). Conclusions: Patients with LPP had a higher risk of various diseases following LPP diagnosis. Close follow-up is needed to optimize comprehensive patient care.

Background: Waist circumference (WC) has become an essential diagnostic marker of metabolic syndrome; however, its accuracy in reflecting insulin resistance remains uncertain, particularly among Asian people who develop metabolic complications at lower levels of adiposity. Methods: We analyzed 20,202 adults (8886 men and 11,316 women) from the Korean National Health and Nutrition Examination Survey (KNHANES) 2015 and 2019–2021. All analyses accounted for the survey sampling weights and the complex survey design. WC, insulin resistance, and β-cell function were assessed using fasting insulin level, HOMA-IR, and HOMA-β. Associations between WC and insulin indices were evaluated using correlation analyses, stratification by WC deciles, and multivariable regression models adjusted for demographic and metabolic covariates. Results: WC was positively associated with HOMA-IR in both sexes (all p < 0.001). In the fully adjusted model, HOMA-IR remained significantly associated with WC [men, β = 0.014 (95% CI, 0.011–0.016); women, β = 0.009 (95% CI, 0.008–0.011)]. Subgroup analyses stratified by age revealed significant associations across all age groups. The association was stronger in older adults, particularly among men, whereas women exhibited significant associations across all ages with a larger age-related increase. Conclusions: WC is independently associated with insulin resistance in Korean adults, with stronger associations in older adults and consistent associations in women. These findings support WC as a simple yet pathophysiologically meaningful marker of metabolic risk and highlight the necessity of refining WC cutoff values for clinical screening of Asian populations and an age-specific approach for diagnosing metabolic syndrome.