RESUMEN
Psoriasis is a chronic inflammatory disorder which is associated with impaired skin barrier function. In this context, it was shown that serum IgE level was elevated in significant proportion of psoriasis patients. However, whether serum IgE levels are associated with treatment outcomes of psoriasis has not been understood. We retrospectively analyzed psoriasis patients who visited our clinics through electromedical records. Patients with history of atopic dermatitis were excluded. Total of 483 patients clinically or pathologically diagnosed with psoriasis vulgaris were included for analyses. Initial mean serum IgE level was 226 ± 490.3 KU/L and patients with IgE higher than upper limit normal value were 42.0% (n = 203). Psoriasis Area and Severity Index (PASI) 75 achievement rate according to IgE elevation was analyzed and no statistically meaningful difference was shown. In addition, logistic regression analysis to find out relationship between PASI 75 achievement and IgE titer also failed to show statistically significant relationship. In conclusion, serum IgE level was elevated in significant proportion in the patients with psoriasis, but its elevated level was not associated with treatment outcome.
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Dermatitis Atópica , Psoriasis , Humanos , Estudios Retrospectivos , Dermatitis Atópica/tratamiento farmacológico , Resultado del Tratamiento , Inmunoglobulina E , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Psoriasis is a chronically relapsing inflammatory skin disease primarily perpetuated by skin-resident IL-17-producing T (T17) cells. Pellino-1 (Peli1) belongs to a member of E3 ubiquitin ligase mediating immune receptor signaling cascades, including nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) pathway. OBJECTIVE: We explored the potential role of Peli1 in psoriatic inflammation in the context of skin-resident T17 cells. METHODS: We performed single-cell RNA sequencing of relapsing and resolved psoriatic lesions with analysis for validation data set of psoriasis. Mice with systemic and conditional depletion of Peli1 were generated to evaluate the role of Peli1 in imiquimod-induced psoriasiform dermatitis. Pharmacologic inhibition of Peli1 in human CD4+ T cells and ex vivo human skin cultures was also examined to evaluate its potential therapeutic implications. RESULTS: Single-cell RNA sequencing analysis revealed distinct T-cell subsets in relapsing psoriasis exhibiting highly enriched gene signatures for (1) tissue-resident T cells, (2) T17 cells, and (3) NF-κB signaling pathway including PELI1. Peli1-deficient mice were profoundly protected from psoriasiform dermatitis, with reduced IL-17A production and NF-κB activation in γδ T17 cells. Mice with conditional depletion of Peli1 treated with FTY720 revealed that Peli1 was intrinsically required for the skin-resident T17 cell immune responses. Notably, pharmacologic inhibition of Peli1 significantly ameliorated murine psoriasiform dermatitis and IL-17A production from the stimulated human CD4+ T cells and ex vivo skin explants modeling psoriasis. CONCLUSION: Targeting Peli1 would be a promising therapeutic strategy for psoriasis by limiting skin-resident T17 cell immune responses.
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Dermatitis , Psoriasis , Ratones , Humanos , Animales , Interleucina-17 , FN-kappa B/metabolismo , Piel , Modelos Animales de Enfermedad , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
BACKGROUND: The phase 3 studies, VOYAGE 1 and 2, were conducted to assess guselkumab in the treatment of patients with moderate-to-severe psoriasis. OBJECTIVES: To investigate the efficacy and safety of guselkumab in Korean patients. METHODS: The Korean sub-population of VOYAGE 1 and 2 study patients were included in this analysis. Efficacy and safety were evaluated through Weeks 24 and 28, respectively. RESULTS: Of 126 randomized Korean patients, 30, 63, and 33 received placebo, guselkumab, and adalimumab, respectively. At Week 16, guselkumab was superior to placebo in achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (cleared or minimal; 90.5 vs. 20.0%, p<.001) and a Psoriasis Area and Severity Index (PASI) 90 response (71.4 vs. 3.3%, p<.001). At week 24, a significantly higher proportion of guselkumab-treated patients achieved PASI 75 and IGA 0 (clear skin) responses compared to adalimumab-treated patients (PASI 75: 93.7 vs. 66.7%, p<.001; IGA 0: 52.4 vs. 21.2%, p=.004). Through Week 28, guselkumab and adalimumab showed comparable safety profiles. CONCLUSION: The efficacy and safety of guselkumab in Korean psoriasis patients through 28 weeks were consistent with findings for the overall VOYAGE 1 and 2 study population.
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Psoriasis , Adalimumab/uso terapéutico , Anticuerpos Monoclonales Humanizados , Método Doble Ciego , Humanos , Psoriasis/tratamiento farmacológico , República de Corea , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Both human and mouse allergic contact dermatitis (ACD) frequently demonstrates a combined type 1 and type 2 immune response. However, the relative importance of type 2 immunity in this setting has been incompletely understood yet. OBJECTIVE: To explore an effector function of type 2 immunity in ACD with mixed type 1/type 2 immune response. METHODS: Gene expression characteristics of contact hypersensitivity (CHS) model was examined by quantitative polymerase chain reaction. Cytokine profile of T cells was analyzed by flow cytometry. The involvement of type 2 immunity was assessed by antibody-mediated cytokine neutralization and cell depletion. The role of specific subset of cutaneous dendritic cells was evaluated using diphtheria toxin-induced cell-depleting mouse strains. RESULTS: Oxazolone-induced CHS revealed a combination of type 1/type 2 gene expression. The severity of oxazolone-induced CHS was ameliorated by neutralization of IL-4 but not of IFN-γ, indicating that type 2 immunity plays a dominant effector function in this mixed type 1/type 2 model. Mechanistically, type 2 effector immunity was mounted by CD301b+Langeirn- dermal dendritic cells in part through thymic stromal lymphopoietin-interleukin 7 receptor alpha signaling-dependent manner. CONCLUSION: Our findings suggest the clinical rationale for targeting type 2 immunity as a relevant therapeutic strategy for the mixed immune phenotype of ACD.
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Células Dendríticas/inmunología , Dermatitis Alérgica por Contacto/genética , Dermatitis Alérgica por Contacto/inmunología , Animales , Antígenos de Superficie/metabolismo , Dermatitis Alérgica por Contacto/patología , Modelos Animales de Enfermedad , Inmunidad/genética , Inmunoglobulinas/metabolismo , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-17/genética , Interleucina-4/genética , Interleucina-4/inmunología , Lectinas Tipo C/metabolismo , Lectinas de Unión a Manosa/metabolismo , Ratones , Oxazolona , Receptores de Citocinas/metabolismo , Transducción de Señal , Piel/patología , Linfocitos T/metabolismo , TranscriptomaRESUMEN
The association between psoriasis and risk of psychiatric diseases has not been thoroughly evaluated in a large longitudinal cohort of the Asian population. We conducted a nationwide cohort study encompassing more than 1.6 million Koreans with a 12-year follow-up period. Patients were considered to be in the psoriasis cohort if they had an incident diagnostic code for psoriasis and included patients were followed up until they developed any psychiatric disease. In adjusted models, psoriasis patients (n = 10 868) were at an 18% increased risk for depression (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.09-1.26), 16% for anxiety disorders (HR, 1.16; 95% CI, 1.08-1.26), and 21% for somatoform disorders (HR, 1.21; 95% CI, 1.08-1.34) compared with the referent cohort (n = 1 620 055). Patients with moderate-to-severe psoriasis had a higher risk of developing depression and somatoform disorders than patient with mild disease (depression, HR, 1.28; 95% CI, 1.07-1.54 vs HR, 1.17; 95% CI, 1.07-1.27; somatoform disorders, HR, 1.60; 95% CI, 1.26-2.03 vs HR, 1.13; 95% CI, 1.00-1.28). Our results highlight the burden of psychiatric diseases in patients with psoriasis in Korea and suggest that appropriate medical support for possible mental illness is warranted in Asian psoriatic patients.
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Trastornos Mentales , Psoriasis , Estudios de Cohortes , Humanos , Incidencia , Trastornos Mentales/epidemiología , Modelos de Riesgos Proporcionales , Psoriasis/epidemiología , República de Corea/epidemiología , Factores de RiesgoRESUMEN
The skin is the outermost barrier organ in the body, which contains several types of dendritic cells (DCs), a group of professional antigen-presenting cells. When the skin encounters invading pathogens, different cutaneous DCs initiate a distinct T cell immune response to protect the body. Among the invading pathogens, fungal infection specifically drives a protective interleukin-17-producing Th17 immune response. A protocol was developed to efficiently differentiate Th17 cells by intradermal Candida albicans infection to investigate a subset of cutaneous DCs responsible for inducing Th17 immunity. Flow cytometry and gene expression analyses revealed a prominent induction of Th17 immune response in skin-draining lymph nodes and infected skin. Using diphtheria toxin-induced DC subset-depleting mouse strains, CD301b+ dermal DCs were found to be responsible for mounting optimal Th17 differentiation in this model. Thus, this protocol provides a valuable method to study in vivo function of differential subsets of cutaneous DCs to determine Th17 immunity against deep skin fungal infection.
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Candida albicans , Células Th17 , Animales , Células Dendríticas , Células de Langerhans , Ratones , Ratones Endogámicos C57BLRESUMEN
Postmarketing surveillance is conducted to establish drug safety and effectiveness under real-world practice. We aimed to validate the effectiveness and safety of ustekinumab in the treatment of adult Korean patients with plaque psoriasis under real-world practice. This was a prospective, observational, and multi-center study. Subjects aged 18 years or older who were treated with ustekinumab for plaque psoriasis were enrolled. We enrolled 977 patients; 654 (66.9%) were men, with mean body surface area (BSA, ± standard deviation) of 27.0 ± 18.3% and mean psoriasis area severity index (PASI) score of 18.1 ± 9.7. The effectiveness analysis was performed in 581 patients who had at least one follow-up assessment and met treatment criteria per local label and reimbursement guidelines. Of these patients, 287 had effectiveness data for visit 6 at 53.7 ± 2.1 weeks. At visit 6, 91.6% (263/287), 51.2% (147/287), and 9.4% (27/287) patients achieved PASI 75, 90, and 100 responses, respectively. Adverse events (AEs) occurred in 112 of the 977 (11.5%) patients with an incidence rate of 21.5 per 100 patient-years (PYs). Serious AEs occurred in eight (0.8%) patients with an incidence rate of 1.2 per 100 PYs. The estimated 1-year drug survival rate was 87.7%. The multiple logistic regression analysis showed that higher baseline PASI score and no prior biologic exposure were significant predictors for PASI 90 response at visit 6. Ustekinumab was effective and safe, and displayed a high survival rate in the treatment of adult Korean patients with plaque psoriasis in real-world practice.
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Psoriasis , Ustekinumab , Adulto , Femenino , Humanos , Masculino , Estudios Prospectivos , Psoriasis/tratamiento farmacológico , República de Corea/epidemiología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Ustekinumab/efectos adversosRESUMEN
Dendritic cells (DCs) are key antigen-presenting cells that prime naive T cells and initiate adaptive immunity. Although the genetic deficiency and transgenic overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) signaling were reported to influence the homeostasis of DCs, the in vivo development of DC subsets following injection of GM-CSF has not been analyzed in detail. Among the treatment of mice with different hematopoietic cytokines, only GM-CSF generates a distinct subset of XCR1-33D1- DCs which make up the majority of DCs in the spleen after three daily injections. These GM-CSF-induced DCs (GMiDCs) are distinguished from classical DCs (cDCs) in the spleen by their expression of CD115 and CD301b and by their superior ability to present blood-borne antigen and thus to stimulate CD4+ T cells. Unlike cDCs in the spleen, GMiDCs are exceptionally effective to polarize and expand T helper type 2 (Th2) cells and able to induce allergic sensitization in response to blood-borne antigen. Single-cell RNA sequencing analysis and adoptive cell transfer assay reveal the sequential differentiation of classical monocytes into pre-GMiDCs and GMiDCs. Interestingly, mixed bone marrow chimeric mice of Csf2rb+/+ and Csf2rb-/- demonstrate that the generation of GMiDCs necessitates the cis expression of GM-CSF receptor. Besides the spleen, GMiDCs are generated in the CCR7-independent resident DCs of the LNs and in some peripheral tissues with GM-CSF treatment. Also, small but significant numbers of GMiDCs are generated in the spleen and other tissues during chronic allergic inflammation. Collectively, our present study identifies a splenic subset of CD115hiCD301b+ GMiDCs that possess a strong capacity to promote Th2 polarization and allergic sensitization against blood-borne antigen.
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Antígenos/inmunología , Células Dendríticas/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Granulocitos/inmunología , Macrófagos/inmunología , Monocitos/inmunología , Bazo/inmunología , Células Th2/inmunología , Animales , Presentación de Antígeno/inmunología , Diferenciación Celular/inmunología , Células Cultivadas , Proteínas de la Membrana/inmunología , Ratones , Ratones Endogámicos C57BL , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunologíaRESUMEN
Fingerprints are unique to primates and koalas but what advantages do these features of our hands and feet provide us compared with the smooth pads of carnivorans, e.g., feline or ursine species? It has been argued that the epidermal ridges on finger pads decrease friction when in contact with smooth surfaces, promote interlocking with rough surfaces, channel excess water, prevent blistering, and enhance tactile sensitivity. Here, we found that they were at the origin of a moisture-regulating mechanism, which ensures an optimal hydration of the keratin layer of the skin for maximizing the friction and reducing the probability of catastrophic slip due to the hydrodynamic formation of a fluid layer. When in contact with impermeable surfaces, the occlusion of the sweat from the pores in the ridges promotes plasticization of the skin, dramatically increasing friction. Occlusion and external moisture could cause an excess of water that would defeat the natural hydration balance. However, we have demonstrated using femtosecond laser-based polarization-tunable terahertz wave spectroscopic imaging and infrared optical coherence tomography that the moisture regulation may be explained by a combination of a microfluidic capillary evaporation mechanism and a sweat pore blocking mechanism. This results in maintaining an optimal amount of moisture in the furrows that maximizes the friction irrespective of whether a finger pad is initially wet or dry. Thus, abundant low-flow sweat glands and epidermal furrows have provided primates with the evolutionary advantage in dry and wet conditions of manipulative and locomotive abilities not available to other animals.
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Dedos/anatomía & histología , Fuerza de la Mano/fisiología , Locomoción/fisiología , Actividad Motora/fisiología , Primates/fisiología , Adulto , Animales , Evolución Biológica , Dermatoglifia , Dedos/diagnóstico por imagen , Dedos/fisiología , Fricción , Humanos , Masculino , Microfluídica , Sudor/química , Sudor/metabolismo , Glándulas Sudoríparas/química , Glándulas Sudoríparas/metabolismo , Tomografía de Coherencia ÓpticaRESUMEN
Glucocorticoids (GCs) are potent anti-inflammatory drugs, the secretion of which is mediated and controlled by the hypothalamic-pituitary-adrenal axis. However, they are also secreted de novo by peripheral tissues for local use. Several tissues express 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1), including the skin. The inactive GC cortisone is converted by 11ß-HSD1 to active GC cortisol, which is responsible for delayed wound healing during a systemic excess of GC. However, the role of 11ß-HSD1 in inflammation is unclear. We assessed whether 11ß-HSD1 affects the development of atopic dermatitis (AD) in vitro and in vivo. The expression of 11ß-HSD1 in the epidermis of AD lesions was higher than that in the epidermis of healthy controls. Knockdown of 11ß-HSD1 in human epidermal keratinocytes increased the production of thymic stromal lymphopoietin. In an oxazolone-induced mouse model of AD, localized inhibition of 11ß-HSD1 aggravated the development of AD and increased serum cytokine levels associated with AD. Mice with whole-body knockout (KO) of 11ß-HSD1 developed significantly worse AD upon induction by oxazolone. We propose that 11ß-HSD1 is a major factor affecting AD pathophysiology via suppression of atopic inflammation due to the modulation of active GC in the skin.
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11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Dermatitis Atópica/metabolismo , Oxazolona/efectos adversos , Regulación hacia Arriba , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/genética , Animales , Estudios de Casos y Controles , Línea Celular , Citocinas/metabolismo , Dermatitis Atópica/inducido químicamente , Modelos Animales de Enfermedad , Epidermis/metabolismo , Epidermis/patología , Femenino , Técnicas de Inactivación de Genes , Humanos , Queratinocitos/citología , Queratinocitos/metabolismo , Ratones , Timo/metabolismoRESUMEN
The association between psoriasis and risk of atherosclerotic cardiovascular disease has not been thoroughly evaluated in a large longitudinal cohort of an Asian population. We conducted a nationwide population-based retrospective cohort study encompassing more than 1.7 million Koreans with a 15-year follow-up period. The period prevalence of psoriasis was 0.33% among the baseline participants (1997-2000). In Cox proportional hazard analyses, the individuals with psoriasis had a higher adjusted hazard ratio (HR) for incidence of overall atherosclerotic cardiovascular disease (HR, 1.18; 95% confidence interval [CI], 1.09-1.27) compared with controls. Subgroup analyses revealed that the risk for myocardial infarction was commonly increased in both sexes with moderate to severe psoriasis (male: HR, 2.09; 95% CI, 1.35-3.24; female: HR, 3.23; 95% CI, 1.34-7.76), whereas the risk for ischemic stroke was specifically increased in female individuals with moderate to severe psoriasis (HR, 2.02; 95% CI, 1.24-3.30). Our data suggest that appropriate medical screening for possible cardiovascular comorbidities is warranted in Asian psoriatic patients according to disease severity and sex.
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Angina de Pecho/epidemiología , Aterosclerosis/epidemiología , Infarto del Miocardio/epidemiología , Psoriasis/epidemiología , Accidente Cerebrovascular/epidemiología , Adulto , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prevalencia , Modelos de Riesgos Proporcionales , Psoriasis/diagnóstico , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores SexualesRESUMEN
The 52-week results from the CLEAR (NCT02074982) study showed high and superior efficacy of secukinumab versus ustekinumab in clearing skin and improving patient-reported outcomes, with comparable safety profile in subjects with moderate to severe psoriasis. Here, we analyzed the efficacy and safety of secukinumab in Asian subjects from the CLEAR study. In this double-blind, phase IIIb study, eligible subjects with moderate to severe plaque psoriasis were randomized (1:1) to receive s.c. injection of secukinumab 300 mg or ustekinumab as per label. Of 62 subjects included in Asian subanalyses, 23 were randomized to secukinumab and 39 to ustekinumab. A significantly higher proportion of subjects achieved 90% or more improvement in Psoriasis Area and Severity Index (PASI 90) with secukinumab versus ustekinumab at week 16 (78.3% vs 35.9%, P = 0.0010) and at week 52 (60.9% vs 33.3%, P = 0.0196). Similarly, a higher proportion of subjects achieved PASI 100 with secukinumab versus ustekinumab at week 16 (43.5% vs 10.3%, P = 0.0029) and at week 52 (30.4% vs 12.8%, P = 0.0704). The median time to achieve 50% improvement in baseline PASI was 2.8 weeks in the secukinumab group versus 6.3 weeks in the ustekinumab group. The safety profile of secukinumab was in line with the known profile and no deaths occurred. Overall, 95.7% and 84.6% of subjects remained on secukinumab and ustekinumab, respectively. Similar to the core study, secukinumab showed sustained and superior efficacy with faster response versus ustekinumab, and no new or unexpected safety concerns were identified, in Asian subjects with moderate to severe plaque psoriasis.
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Anticuerpos Monoclonales/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Psoriasis/tratamiento farmacológico , Ustekinumab/administración & dosificación , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Pueblo Asiatico , Fármacos Dermatológicos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Psoriasis/diagnóstico , Psoriasis/patología , Índice de Severidad de la Enfermedad , Piel/efectos de los fármacos , Piel/patología , Factores de Tiempo , Ustekinumab/efectos adversosAsunto(s)
Conexinas/genética , Enfermedad de Darier/diagnóstico , Conexina 26 , Enfermedad de Darier/genética , Humanos , Lactante , Masculino , MutaciónAsunto(s)
Células Dendríticas/patología , Epidermis/patología , Células de Langerhans/metabolismo , Células de Langerhans/patología , Desequilibrio Hidroelectrolítico/metabolismo , Análisis de Varianza , Animales , Biopsia con Aguja , Células Dendríticas/citología , Modelos Animales de Enfermedad , Epidermis/fisiopatología , Inmunohistoquímica , Técnicas In Vitro , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Permeabilidad , Distribución Aleatoria , Valores de Referencia , Absorción Cutánea/fisiologíaRESUMEN
BACKGROUND: Psoriasis and psoriatic arthritis (PsA) are included in the group of immune-mediated inflammatory diseases (IMIDs) caused by systemic inflammation; however, indicators for monitoring inflammatory activity in patients with psoriasis, such as the Psoriasis Area and Severity Index (PASI), are limited. OBJECTIVE: To determine whether the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire can be used to monitor disease activity in patients with psoriasis. METHODS: This was a multicenter, noninterventional, cross-sectional study. Demographic factors and PASI and PASE scores were collected to investigate associations between each. RESULTS: PASE data were available for 1,255 patients, of whom 498 (39.7%) had a score of ≥37. Compared with the group with PASE score <37, the group with score ≥37 had a higher proportion of women (34.9% vs. 48.8%, p<0.0001), older mean age at diagnosis (36.4 vs. 41.7 years, p<0.0001), more severe disease activity using PASI and body surface area measures (p=0.0021 and p=0.0008, respectively), and higher mean body mass index (23.7 vs. 24.1, p=0.0411). In a multiple linear regression model, PASE score was positively associated with cutaneous disease activity (p<0.0001). CONCLUSION: After risk-adjustment, PASE was positively associated with PASI, which suggests that PASE can be sensitive to disease activity. Since psoriasis is regarded as one of the IMIDs, PASE may be utilized as a tool not only to screen PsA but also to monitor disease activity.
RESUMEN
BACKGROUND: Langerhans cells (LCs) are dendritic cells that reside in the epidermis and local inflammation results in an increased differentiation of monocyte-derived LCs. Only few studies have investigated on the role of LCs in psoriasis-like dermatitis model, but the results are variable and the exact role of LCs in psoriasis model remains to be elucidated. OBJECTIVE: To explore the functional role of resident (rLCs) and monocyte-derived LCs (mLCs) in imiquimod (IMQ)-induced psoriasis-like inflammation using human Langerin-diphtheria toxin subunit A (huLang-DTA) mice. METHODS: 5% IMQ cream was topically applied on the skins. Clinical and histopathological features were evaluated. Psoriasis-related gene expression was analyzed by quantitative polymerase chain reaction. The production of psoriasis-related cytokines including IL-17A and IL-22 by T cells were assessed by flow cytometry from the lesional skins. RESULTS: huLang-DTA mice showed a common depletion of both rLCs and mLCs in the IMQ-treated skins. huLang-DTA mice had a reduced IMQ-induced psoriasis-like inflammation featuring erythema, scale, and thickness compared with wild-type mice. Psoriatic lesions from huLang-DTA mice had a decreased level of Il23a and accordingly demonstrated an attenuated cytokine production of IL-17A and IL-22 from γδlow T cells. mLCs revealed a significantly greater level of IL-23 expression compared to rLCs in response to topical IMQ treatment. CONCLUSION: Although both rLCs and mLCs are involved in the development of IMQ-induced psoriasis-like dermatitis, inflammation-induced mLCs present a superior capacity for producing IL-23 in this murine experimental model of psoriasis.
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Citocinas/metabolismo , Células de Langerhans/inmunología , Psoriasis/inmunología , Aminoquinolinas/inmunología , Animales , Antígenos CD/genética , Citocinas/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Modelos Animales de Enfermedad , Células Epidérmicas , Epidermis/inmunología , Epidermis/metabolismo , Epidermis/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Imiquimod , Células de Langerhans/metabolismo , Lectinas Tipo C/genética , Masculino , Lectinas de Unión a Manosa/genética , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Monocitos/fisiología , Psoriasis/patologíaRESUMEN
Yonsei Dermatology celebrated its centennial in 2017, marking 100 years since Kung Sun Oh established the first Department of Dermatology and Urology in Korea in 1917. Following the footsteps of Kung Sun Oh, a pioneer of Korean dermatology, its members united and worked to provide the best medical service and achieve academic milestones in dermatology. Over the past hundred years, Yonsei Dermatology has played a pivotal role in the advancement of medical science and academia in Korea. The main activities of the department include medical care, education, and dermatologic research. Its research activities have encompassed a wide spectrum of dermatologic manifestations from skin immunology and pathology to introduction of newly developed treatment technologies. As Kung Sun Oh was the first Korean professor of dermatology at Severance Medical School and a passionate educator, we continue to serve his will by nurturing medical students and dermatology specialists to serve as global medical leaders. The Kung Sun Oh Memorial Lecture, first hosted in 1977, was the beginning of mutual international academic exchange in the field of dermatology in Korea. The memorial lecture has played a major role in advancing the academic status of Korean dermatological science by inviting distinguished dermatologists from around the world as guest lecturers. Yonsei Dermatology has played a key role in the history of modern medicine and dermatology in Korea over the last 100 years and continues to make an impact.
RESUMEN
Psoriasis is largely mediated by interleukin (IL)-23/T helper (Th) 17 axis, and IL-21 is a pleiotropic cytokine expressed by Th17 cells. Despite previously reported possible pathogenic roles of IL-21 in human psoriasis, we found that IL-21 receptor (IL-21R) signalling was not crucial for imiquimod-induced psoriatic inflammation, using IL-21R-/- mice. The severity of imiquimod-induced psoriatic manifestation and pro-inflammatory Th17 cytokine levels, IL-17A-producing γδ T cells and CD4+ T cells, and in vitro IL-17A production by γδ T cells after IL-23 stimulation was comparable between wild-type and IL-21R-/- mice. Collectively, IL-21R signalling was not critically involved in IMQ-induced psoriatic inflammation despite an increased IL-21 expression in the IMQ-treated mouse skin. Our data may represent the significant differences between human psoriasis and murine psoriasis model, and further studies using other models will be required to elucidate the role of IL-21 in psoriasis pathogenesis.
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Dermatitis/genética , Subunidad alfa del Receptor de Interleucina-21/metabolismo , Psoriasis/genética , Receptores de Interleucina-21/metabolismo , Animales , Linfocitos T CD4-Positivos/citología , Dermatitis/metabolismo , Imiquimod , Inflamación , Inductores de Interferón/farmacología , Subunidad alfa del Receptor de Interleucina-21/genética , Subunidad p19 de la Interleucina-23/metabolismo , Linfocitos Intraepiteliales/citología , Ratones , Ratones Noqueados , Ratones Transgénicos , Psoriasis/inducido químicamente , Psoriasis/metabolismo , Receptores de Interleucina-21/genética , Transducción de SeñalRESUMEN
Knowledge of the clinical course of chronic spontaneous urticaria (CSU) remains unclear. The purpose of our study was to investigate the clinical course of CSU in the Korean adult population. Each patient in the CSU group who was defined by disease codes between 2003 and 2007 was tracked whether he or she went into remission or not until 2013. Kaplan-Meier survival analysis was carried out to analyze remission, and log-rank tests were performed for between-group comparisons. Demographic differences between subjects who went into remission 1 year after the initial diagnosis and those who did not were analyzed using χ² tests. A total of 13,969 subjects were included in the CSU group. The 1-, 2-, 3-, 4-, and 5-year remission rates of CSU were 21.5%, 33.0%, 38.9%, 42.6%, and 44.6%, respectively. The proportion of subjects in the 65+ age group (P=0.050) and with male gender (P=0.002) was significantly higher among subjects who did not go into remission 1 year after the initial diagnosis. Our study indicates that CSU could have a more persistent course than previously reported.
RESUMEN
Conventional dendritic cells (cDCs) are composed of heterogeneous subsets commonly arising from dendritic cell (DC)-committed progenitors. A population of CD301b-expressing DCs has recently been identified in non-lymphoid barrier tissues such as skin. However, whether CD301b+ DCs in the skin represent an ontogenetically unique subpopulation of migratory cDCs has not been fully addressed. Here, we demonstrated that CD301b+ dermal DCs were distinct subpopulation of FMS-like tyrosine kinase 3 ligand (FLT3L)-dependent CD11b+ cDC2 lineage, which required an additional GM-CSF cue for the adequate development. Although the majority of lymphoid-resident cDC2 lacked CD301b expression, dermal migratory cDC2 contained a substantial fraction of CD301b+ subset. Similar to CD301b- population, CD301b+ dermal DC development was closely regulated by FLT3 signaling, suggesting their common origin from FLT3L-responsive cDC progenitors. However, FLT3L-driven cDC progenitor culture was not sufficient, but additional GM-CSF treatment was required to produce CD301b+ cDC2. In vivo development of CD301b+ cDC2 was significantly augmented by exogenous GM-CSF, while the repopulation of CD301b+ dermal cDC2 was abrogated by GM-CSF neutralization. Functionally, CD301b+ cDC2 was capable of producing a high level of IL-23, and the depletion of CD301b+ cDC2 effectively prevented IL-17-mediated psoriasiform dermatitis. Therefore, our findings highlight the differentiation program of a distinct CD301b+ dermal cDC2 subset in the skin and its involvement in psoriatic inflammation.