1.MOR106 alleviates inflammation in mice with atopic dermatitis by blocking the JAK2/STAT3 signaling pathway and inhibiting IL-17C-mediated Tfh cell differentiation.
Limin TIAN ; Xiaohui HUYAN ; Sen YANG ; Mengjie WANG ; Yuenan YANG
Chinese Journal of Cellular and Molecular Immunology 2024;40(1):26-32
Objective To explore the significance of interleukin-17C(IL-17C)-mediated follicular helper T cell (Tfh) differentiation in atopic dermatitis (AD) model. Methods BALB/c mice were divided into control group, AD model group, low-dose MOR106 (anti-IL-17C huIgG1)(MDR106-L)treatment group and high-dose MOR106 (MOR106-H) treatment group, 8 mice in each group. Except for the control group, all the other groups were treated with 2, 4- dinitrochlorobenzene (DNCB) to establish AD models. The low-dose and high-dose MOR106 groups were treated with 5 mg/kg or 10 mg/kg MOR106 respectively. The differentiation of Tfh cell subsets in peripheral blood of mice was analyzed by flow cytometry, and the expression of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signal pathway protein in skin tissue was detected by Western blot analysis. Results Compared with the control group, the dermatitis severity score, mass difference between two ears, spleen mass and spleen index of DNCB group increased significantly, while those of MOR106-L group and MOR106-H group decreased significantly. Compared with the control group, the Tfh subgroup of AD mice showed deregulated differentiation, resulting in a significant increase in the percentage of CD4+CXCR5+IFN-γ+Tfh1 cells, CD4+CXCR5+IL-17A+Tfh17 and CD4+CXCR5+IL-21+Tfh21 cells, and a significant decrease in the percentage of CD4+CXCR5+IL-10+Tfh10 cells and CD4+CXCR5+FOXP3+Tfr cells in peripheral blood. The protein levels of phosphorylated JAK2(p-JAK2) and p-STAT3 were significantly increased. MOR106 effectively reversed these changes of Tfh1, Tfh10, Tfh17, Tfh21 and Tfr cells in peripheral blood of AD mice. Compared with AD group, the levels of p-JAK2 and p-STAT3 protein in low-dose and high-dose MOR106 treatment groups decreased significantly. Conclusion MOR106 can reduce the inflammatory response of AD mice by blocking JAK2/STAT3 signaling pathway and inhibiting the differentiation of Tfh cells mediated by IL-17C.
Animals
;
Mice
;
Dermatitis, Atopic/drug therapy*
;
Interleukin-17
;
T Follicular Helper Cells
;
Janus Kinase 2
;
Dinitrochlorobenzene
;
Inflammation
;
Cell Differentiation
;
Signal Transduction
3.Validation study of the Chinese version of atopic dermatitis control tool.
Ting Ting LUAN ; Cheng Yue PENG ; Xiao Ting SONG ; Shuang Lu LIAO ; Zuo Tao ZHAO
Chinese Journal of Preventive Medicine 2023;57(3):422-426
To assess the reliability, validity and responsiveness of the Chinese version of the atopic dermatitis control tool (ADCT). After this study obtained authorization for the Chinese version of the ADCT scale. 114 patients with atopic dermatitis were enrolled from the Department of Dermatology, Peking University First Hospital using convenience sampling from October 2022. Patients were surveyed using the General Information Questionnaire, Chinese version of ADCT, patient-oriented eczema measure (POEM),peak pruritus numerical rating scale (PP-NRS),dermatology life quality index (DLQI) and the global patient self-assessment for disease severity. Mann-Whitney rank sum test and Spearman correlation analysis were used for item analysis; content validity was assessed using content validity index (CVI); exploratory factor analysis was used to assess structural validity; Cronbach' alpha coefficient was used to assess internal consistency; Spearman correlation analysis was used to assess the correlation of ADCT with other scales to assess external responsiveness. The results showed that all items were retained by item analysis. I-CVI was 0.9-1, and S-CVI/Average was 0.983; the scale extracted one common factor by factor analysis, the cumulative variance explanation rate was 77.927%; the Cronbach' alpha coefficient of the scale was 0.937; the correlation coefficients of the Chinese version of ADCT with POEM, PP-NRS, and DLQI were 0.805, 0.861, and 0.709 respectively. In conclusion, the Chinese version of the ADCT has adequate reliability, validity and responsiveness, and is suitable for measuring disease control in Chinese patients with atopic dermatitis.
Humans
;
Dermatitis, Atopic
;
Quality of Life
;
Reproducibility of Results
;
Surveys and Questionnaires
4.A multi-center, double-blind, randomized, placebo- and positive-controlled phase II clinical study of benvitimod for the treatment of atopic dermatitis.
Lin CAI ; Yan ZHAO ; Min ZHENG ; Furen ZHANG ; Qing SUN ; Quanzhong LIU ; Jin HU ; Juan SHEN ; Jianzhong ZHANG
Chinese Medical Journal 2023;136(2):251-252
5.Ozonated oil alleviates dinitrochlorobenzene-induced allergic contact dermatitis via inhibiting the FcεRI/Syk signaling pathway.
Zhibing FU ; Yajie XIE ; Liyue ZENG ; Lihua GAO ; Xiaochun YU ; Lina TAN ; Lu ZHOU ; Jinrong ZENG ; Jianyun LU
Journal of Central South University(Medical Sciences) 2023;48(1):1-14
OBJECTIVES:
Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms.
METHODS:
Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions.
RESULTS:
Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1β, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1β, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05).
CONCLUSIONS
Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.
Animals
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Mice
;
Dinitrochlorobenzene/metabolism*
;
Skin/metabolism*
;
Cytokines/metabolism*
;
Interleukin-17/metabolism*
;
Tumor Necrosis Factor-alpha/metabolism*
;
Dermatitis, Allergic Contact/pathology*
;
Dermatitis, Atopic/chemically induced*
;
Signal Transduction
;
RNA, Messenger/metabolism*
;
Mice, Inbred BALB C
6.Advances in Diagnostic Criteria and Severity Assessment of Atopic Dermatitis.
Acta Academiae Medicinae Sinicae 2023;45(3):493-499
Atopic dermatitis(AD),a chronic and relapsing skin disease,is characterized by dry skin and pruritus,severely affecting the quality of patients' life.Accurately grasping the diagnostic criteria and severity assessment is essential and helps to avoid misdiagnosis and missed diagnosis.Moreover,it facilities the development and adjustment of the therapeutic schedule according to the therapeutic reaction and disease control conditions.This article reviews the research advances in the diagnostic criteria and severity assessment of AD.
Humans
;
Dermatitis, Atopic/drug therapy*
;
Pruritus
;
Skin Diseases
;
Severity of Illness Index
7.Maternal nutritional factors and environmental exposure in early life and childhood atopic dermatitis.
Ying YE ; Li Min DOU ; Liu Hui WANG
Chinese Journal of Preventive Medicine 2023;57(9):1489-1496
Atopic dermatitis(AD)is a chronic, recurrent, inflammatory skin disease in children. The disease is characterized by dryness, chronic eczema-like lesions and obvious itching, seriously affecting the quality of life of children and their families. The pathogenesis of AD is not yet to be clear, and it might be the interaction of genetic susceptibility and environmental exposure to induce skin barrier impairment and immune system dysfunction. In recent years, the role of maternal factors or intrauterine environment exposure on childhood allergic diseases has been attracted attention, and the hypothesis that allergic diseases originate from the fetal period has been postulated. Maternal exposures called "early life exposure", such as nutritional factors during pregnancy (folate, vitamin D, vitamin E and polyunsaturated fatty acid) and tobacco exposure, home environmental exposure may be related with childhood atopic dermatitis. This article would focus on the recent research about maternal nutritional factors and family environmental exposure during pregnancy on offspring's atopic dermatitis.
Child
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Female
;
Pregnancy
;
Humans
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Dermatitis, Atopic
;
Quality of Life
;
Environmental Exposure/adverse effects*
;
Maternal Exposure/adverse effects*
;
Family
8.Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis.
Cheng Yuan LI ; Shuang CHEN ; Wei Lu QIAN ; Liu YANG ; Qiu ZHENG ; Ai Jun CHEN ; Jin CHEN ; Kun HUANG ; Sheng FANG ; Ping WANG ; Li HU ; Xin Ran LIU ; Xiao Qin ZHAO ; Na TAN ; Tao CAI
Chinese Journal of Preventive Medicine 2023;57(10):1590-1595
To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.
Humans
;
Dermatitis, Atopic/drug therapy*
;
Quality of Life
;
Retrospective Studies
;
Severity of Illness Index
;
Treatment Outcome
9.Analysis of clinical characteristics and treatment status of atopic dermatitis in a children's hospital in Beijing from 2015 to 2019.
Chun Ping SHEN ; Yuan LIANG ; Ying LIU ; Lei JIAO ; Jing TIAN ; Yang WANG ; Shan WANG ; Mu Tong ZHAO ; Nan DANG ; Lin MA
Chinese Journal of Preventive Medicine 2023;57(11):1848-1854
To analyze the clinical characteristics and treatment status of atopic dermatitis (AD) in children in the outpatient department of a children's hospital in Beijing from 2015 to 2019. This study used a cross-sectional study method to retrospectively analyze the data of AD patients who visited the Dermatology outpatient department of Beijing Children's Hospital, Capital Medical University, from April 2015 to April 2019. A total of 1 926 AD patients aged 0-17.5 years old living in Beijing and its surrounding areas were included, and the general situation, severity and distribution of AD disease, clinical characteristics and severity of AD, relevant influencing factors of AD onset, AD disease prognosis and treatment status were recorded. SAS 9.4, SPSS19.0, and R software were used for data processing, and descriptive statistical analysis, Chi-square test, Analysis of Variance, and correspondence analysis were used for statistical analysis. The results showed that the male to female ratio of AD patients in children included in this study was 1.4∶1; 79.0% (1 522/1 926), 86.1%(1 658/1 926), 91.3%(1 758/1 926), and 97.3%(1 907/1 926) of AD onset at the age of 6 months, 1 year, 2 years, and 5 years, respectively; mild of AD patients accounted for 13.2% (255/1 926)(SCORAD score 0-24), moderate of AD patients accounted for 50.1%(965/1 926) (SCORAD score 25-50), and severe of AD patients accounted for 36.7% (706/1 926)(SCORAD score>50).The age of severe AD patients were younger than mild and moderate AD patients. The face, head, trunk, and lower limbs were common areas of onset for moderate to severe AD, while the hands, feet, and ears were common areas of onset for severe AD patients. Temperature changes, hot water factors, mental and emotional states, and spring and winter were the main aggravation factors of AD;35.2% (678/1 926) aggravated and 61.8% (1 191/1 926) persistent. The more frequent bathing, the less severity of AD disease (χ2=29.791,P<0.001); 28.0% (520/1 856) of AD patients have no moisturizing habits, which were correlated with the severity of AD disease (χ2=15.908, P<0.05); the proportion of combined treatment medications in children with moderate to severe AD was significantly higher than mild AD patients. In conclusion, the patients with AD who went to specialist clinics were mainly moderate to severe patients and developed disease before the age of 5 years from 2015 to 2019.The severity of AD were mainly moderate to severe, and most of these patients had poor disease control. Traditional treatment plans had limitations. Identifying the clinical characteristics and treatment status of childhood AD would help us to carry out more targeted prevention and management work.
Humans
;
Child
;
Male
;
Female
;
Infant, Newborn
;
Infant
;
Child, Preschool
;
Adolescent
;
Dermatitis, Atopic/psychology*
;
Cross-Sectional Studies
;
Retrospective Studies
;
Severity of Illness Index
;
Hospitals
;
Quality of Life
10.Research progress on the intrinsic relationship and mechanism between respiratory allergies and skin allergies.
Chinese Journal of Preventive Medicine 2023;57(12):1929-1935
Allergic disease is a systemic disease that affects multiple systems. Respiratory tract and skin are the most frequently involved organs of allergies, which include allergic rhinitis, asthma, acute and chronic urticaria, atopic dermatitis, etc.. They are closely correlated clinically. Respiratory allergies and skin allergies often occur in one patient in the form of synchronous occurrence, synchronous aggravation or mutual transfer of symptoms, and early atopic dermatitis in infants is an independent risk factor of respiratory allergy. Type Ⅰ hypersensitivity is the most common immunologic mechanism of respiratory and skin allergies, which are mediated by allergens induction, multiple immune cells and inflammatory cells involvement, and IgE medicated mast cell degranulation. This present article provides a brief review on the epidemiology, tissue origin, and pathogenesis of respiratory airway allergy and skin allergy, in order to provide new ideas and reference basis for clinical diagnosis and treatment and the development of allergic disease prevention strategies.
Infant
;
Humans
;
Dermatitis, Atopic
;
Asthma
;
Rhinitis, Allergic
;
Risk Factors

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