Journal of dermatological science最新文献

英文中文

Serum inflammatory biomarkers associated with disease severity and response to dupilumab treatment in bullous pemphigoid: A cluster analysis 与大疱性类天疱疮疾病严重程度和对杜匹单抗治疗反应相关的血清炎症生物标志物：聚类分析

IF 4.6

Journal of dermatological science

Pub Date : 2024-10-01 DOI: 10.1016/j.jdermsci.2024.09.003

Jiaqi Li , Xixue Chen , Xuejun Zhu , Panpan Shang , Mingyue Wang

Background

Dupilumab, a novel therapy targeting the T helper (Th) 2-mediated inflammation, is showing clinical benefits in treating bullous pemphigoid (BP). However, limited research investigated the serum biomarkers that reflect the inflammation alterations throughout the disease course.

Objectives

To explore the changes of the serum inflammatory biomarkers under dupilumab therapy in BP and establish their correlations with disease severity and clinical outcomes.

Methods

This exploratory study evaluated serum samples from 40 patients with BP at baseline, 30 of these patients following 16-week dupilumab therapy, and 20 senior healthy controls. Serum levels of 29 cytokines and chemokines were quantified using the Magnetic Luminex Assay.

Results

Two distinct clusters based on serum inflammatory profiles were identified. The first cluster, characterized by elevated levels of inflammatory activation, exhibited worse disease severity and poorer remission outcomes. Following the 16-week dupilumab therapy regimen, a significant suppression of Th2-mediated inflammation in the serum was observed, alongside a relative upregulation of Th1 responses. Patients treated with adjuvant systemic steroids exhibited an enhanced suppression of B cell activating factor compared to those receiving dupilumab alone. Significant correlations were unveiled between Th2 biomarkers and clinical scores, eosinophil counts, and anti-BP180 immunoglobulin G levels. Baseline levels of CCL18, Periostin, interleukin (IL)-6, and IL-16 constitute an optimal combination to distinguish between inflammatory clusters.

Conclusions

Cluster analysis of serum inflammatory biomarkers provided novel insights into the heterogeneity of the inflammation profiles in BP. Baseline levels of CCL18, Periostin, IL-6, IL-16 emerged as effective predictors for disease severity and therapy response to dupilumab.

背景：Dupilumab是一种针对T辅助细胞（Th）2介导的炎症的新型疗法，在治疗大疱性类天疱疮（BP）方面显示出临床疗效。然而，对反映整个病程中炎症变化的血清生物标志物的研究却很有限：目的：探讨杜匹单抗治疗大疱性类天疱疮时血清炎症生物标志物的变化，并确定其与疾病严重程度和临床结果的相关性：这项探索性研究评估了 40 名 BP 患者基线时的血清样本、其中 30 名患者接受 16 周杜匹单抗治疗后的血清样本以及 20 名资深健康对照者的血清样本。使用 Magnetic Luminex Assay 对 29 种细胞因子和趋化因子的血清水平进行了量化：结果：根据血清炎症特征确定了两个不同的群组。第一组的特点是炎症激活水平升高，疾病严重程度更严重，缓解效果更差。在接受为期16周的dupilumab治疗后，观察到血清中Th2介导的炎症明显抑制，同时Th1反应相对上调。与单独接受杜比单抗治疗的患者相比，接受辅助性全身类固醇治疗的患者表现出更强的B细胞活化因子抑制能力。Th2生物标记物与临床评分、嗜酸性粒细胞计数和抗BP180免疫球蛋白G水平之间存在显著相关性。CCL18、Periostin、白细胞介素（IL）-6和IL-16的基线水平是区分炎症集群的最佳组合：血清炎症生物标志物的聚类分析为了解血压炎症特征的异质性提供了新的视角。CCL18、Periostin、IL-6、IL-16的基线水平可有效预测疾病的严重程度和对dupilumab的治疗反应。

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引用次数: 0

Recombinant human thioredoxin ameliorates imiquimod-induced psoriasis-like dermatitis in mice 重组人硫氧还蛋白可改善咪喹莫特诱导的小鼠银屑病样皮炎。

IF 4.6

Journal of dermatological science

Pub Date : 2024-10-01 DOI: 10.1016/j.jdermsci.2024.07.002

Alshimaa Mostafa , Kenji Sakurai , Teruasa Murata , Teruki Dainichi , Hai Tian , Junji Yodoi , Kenji Kabashima

引用次数: 0

Editors choice 编辑推荐

IF 4.6

Journal of dermatological science

Pub Date : 2024-10-01 DOI: 10.1016/S0923-1811(24)00207-X

引用次数: 0

Ferrostatin-1 alleviates skin inflammation and inhibits ferroptosis of neutrophils and CD8+ T cells in allergic contact dermatitis 铁前列素-1 可减轻过敏性接触性皮炎的皮肤炎症反应，并抑制中性粒细胞和 CD8+ T 细胞的铁凋亡。

IF 4.6

Journal of dermatological science

Pub Date : 2024-10-01 DOI: 10.1016/j.jdermsci.2024.08.004

Yangying Ke, Ni Lian, Yujie Chen, Yiqun Zhang, Yuancheng Li, Wenlan Zhang, Hui Yu, Heng Gu, Xu Chen

Background

Ferroptosis is considered as an immunogenic type of regulated cell death and associated with the pathogenesis of inflammatory skin diseases. However, the involvement and function of ferroptosis in allergic contact dermatitis (ACD) remains unknown.

Objective

To explore the role of ferroptosis in ACD. To reveal which type of cells develops ferroptosis in ACD.

Methods

We detected the key markers of ferroptosis in 1-Chloro-2,4-dinitrochlorobenzene (DNCB)-induced ACD mice model. We applicated ferrostatin-1 (Fer-1) to restrain ferroptosis in ACD mice and then compared the severity of dermatitis and the level of inflammation and ferroptosis in dermis and epidermis, respectively. Keratinocyte-specific Gpx4 conditional knockout (cKO) mice were used to investigate the function of keratinocyte ferroptosis in the development of ACD. Single-cell RNA sequencing was conducted to analyze the affection of Fer-1 on different type of cells in ACD.

Results

Ferroptosis was involved in DNCB-induced ACD mice. Ferroptosis activation was more remarkable in dermis rather than in epidermis. Gpx4 cKO mice showed similar severity of skin dermatitis as control mice. Fer-1 alleviated skin inflammation in mice and reduced ferroptosis in neutrophils and CD8⁺ T cells both of which contribute to development of ACD.

Conclusion

Ferroptosis was activated in immune cells, especially neutrophils and CD8⁺ T cells in DNCB-induced ACD mice. Fer-1 treatment inhibited ferroptosis of neutrophils and CD8⁺ T cells and relieved skin damage in ACD mice.

背景：铁蛋白沉积被认为是一种调节细胞死亡的免疫原性类型，与炎症性皮肤病的发病机制有关。然而，过敏性接触性皮炎（ACD）中铁细胞凋亡的参与和功能仍不清楚：目的：探讨嗜铁细胞增多症在过敏性接触性皮炎中的作用。揭示在 ACD 中哪种类型的细胞会发生铁蛋白沉积：方法：我们在 1-氯-2,4-二硝基氯苯（DNCB）诱导的 ACD 小鼠模型中检测了铁变态反应的关键标志物。我们使用铁前列素-1（Fer-1）抑制ACD小鼠的铁蛋白沉积，然后比较皮炎的严重程度以及真皮和表皮的炎症和铁蛋白沉积水平。用角质细胞特异性Gpx4条件性基因敲除（cKO）小鼠来研究角质细胞铁突变在ACD发病中的功能。通过单细胞RNA测序分析了Fer-1对ACD中不同类型细胞的影响：结果：铁突变参与了 DNCB 诱导的 ACD 小鼠。结果：铁凋亡参与了 DNCB 诱导的 ACD 小鼠，铁凋亡激活在真皮层比在表皮层更显著。Gpx4 cKO 小鼠皮肤皮炎的严重程度与对照组小鼠相似。Fer-1减轻了小鼠的皮肤炎症，减少了中性粒细胞和CD8+ T细胞中的铁突变，而这两种细胞都会导致ACD的发生：结论：在 DNCB 诱导的 ACD 小鼠中，免疫细胞，尤其是中性粒细胞和 CD8+ T 细胞中的铁蛋白沉积被激活。Fer-1 治疗可抑制中性粒细胞和 CD8+ T 细胞的铁突变，缓解 ACD 小鼠的皮肤损伤。

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引用次数: 0

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IF 4.6

Journal of dermatological science

Pub Date : 2024-10-01 DOI: 10.1016/S0923-1811(24)00204-4

引用次数: 0

Corrigendum to “Decreased TET2/5-hmC reduces the integrity of the epidermal barrier via epigenetic dysregulation of filaggrin in psoriatic lesions” [J. Dermatol. Sci. 113 (2024) 103–112] 对 "银屑病皮损中 TET2/5-hmC 的减少通过丝胶蛋白的表观遗传失调降低了表皮屏障的完整性 "的更正 [J. Dermatol. Sci.

IF 4.6

Journal of dermatological science

Pub Date : 2024-09-01 DOI: 10.1016/j.jdermsci.2024.07.003

Huan Zhang , Tao Jia , Delu Che , Bin Peng , Zhaowei Chu , Xiangjin Song , Weihui Zeng , Songmei Geng

引用次数: 0

Revealing the UV response of melanocytes in xeroderma pigmentosum group A using patient-derived induced pluripotent stem cells 利用源自患者的诱导多能干细胞揭示 A 组色素性角化症黑色素细胞的紫外线反应。

IF 4.6

Journal of dermatological science

Pub Date : 2024-09-01 DOI: 10.1016/j.jdermsci.2024.06.004

Chihiro Takemori , Michiyo Koyanagi-Aoi , Takeshi Fukumoto , Makoto Kunisada , Kazumasa Wakamatsu , Shosuke Ito , Chieko Hosaka , Seiji Takeuchi , Akiharu Kubo , Takashi Aoi , Chikako Nishigori

Background

Xeroderma pigmentosum (XP) is characterized by photosensitivity that causes pigmentary disorder and predisposition to skin cancers on sunlight-exposed areas due to DNA repair deficiency. Patients with XP group A (XP-A) develop freckle-like pigmented maculae and depigmented maculae within a year unless strict sun-protection is enforced. Although it is crucial to study pigment cells (melanocytes: MCs) as disease target cells, establishing MCs in primary cultures is challenging.

Objective

Elucidation of the disease pathogenesis by comparison between MCs differentiated from XP-A induced pluripotent stem cells (iPSCs) and healthy control iPSCs on the response to UV irradiation.

Methods

iPSCs were established from a XP-A fibroblasts and differentiated into MCs. Differences in gene expression profiles between XP-A-iPSC-derived melanocytes (XP-A-iMCs) and Healthy control iPSC-derived MCs (HC-iMCs) were analyzed 4 and 12 h after irradiation with 30 or 150 J/m² of UV-B using microarray analysis.

Results

XP-A-iMCs expressed SOX10, MITF, and TYR, and showed melanin synthesis. Further, XP-A-iMCs showed reduced DNA repair ability. Gene expression profile between XP-A-iMCs and HC-iMCs revealed that, numerous gene probes that were specifically upregulated or downregulated in XP-A-iMCs after 150-J/m² of UV-B irradiation did not return to basal levels. Of note that apoptotic pathways were highly upregulated at 150 J/m² UV exposure in XP-A-iMCs, and cytokine-related pathways were upregulated even at 30 J/m² UV exposure.

Conclusion

We revealed for the first time that cytokine-related pathways were upregulated even at low-dose UV exposure in XP-A-iMCs. Disease-specific iPSCs are useful to elucidate the disease pathogenesis and develop treatment strategies of XP.

背景：色素性皮肤病（XP）的特点是对光敏感，会导致色素失调，并且由于 DNA 修复缺陷，暴露在阳光下的部位容易患皮肤癌。XP A 组（XP-A）患者除非严格执行防晒措施，否则会在一年内出现雀斑样色素斑和色素沉着斑。虽然研究作为疾病靶细胞的色素细胞（黑素细胞：MCs）至关重要，但在原代培养物中建立 MCs 却具有挑战性：方法：从 XP-A 成纤维细胞建立 iPSCs 并分化成 MCs。结果：XP-A-iPSC衍生的黑色素细胞（XP-A-iMCs）和健康对照iPSC衍生的MCs（HC-iMCs）在接受30或150 J/m2的UV-B照射4和12小时后，基因表达谱的差异通过微阵列分析进行了分析：结果：XP-A-iMCs表达SOX10、MITF和TYR，并显示黑色素合成。此外，XP-A-iMCs 的 DNA 修复能力下降。XP-A-iMCs与HC-iMCs的基因表达谱显示，在150-J/m2的UV-B照射后，XP-A-iMCs中特异性上调或下调的许多基因探针并没有恢复到基础水平。值得注意的是，在 150 J/m2 紫外线照射下，XP-A-iMCs 中的凋亡通路被高度上调，而细胞因子相关通路即使在 30 J/m2 紫外线照射下也被上调：我们首次发现，即使在低剂量紫外线照射下，细胞因子相关通路也会在 XP-A-iMCs 中上调。疾病特异性iPSCs有助于阐明XP的疾病发病机制和制定治疗策略。

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引用次数: 0

Cold shock therapy promotes hair growth in association with upregulation of cold-inducible RNA-binding protein and vascular endothelial growth factor 冷休克疗法促进毛发生长与冷诱导 RNA 结合蛋白和血管内皮生长因子的上调有关。

IF 4.6

Journal of dermatological science

Pub Date : 2024-09-01 DOI: 10.1016/j.jdermsci.2024.08.001

Seunghee Lee , Sanseul Kim , Sungjoo Tommy Hwang , Gun-Ho Kim , Ohsang Kwon

引用次数: 0

Corrigendum to “Dual effect of tacrolimus on mast cell-mediated allergy and inflammation through MAS-related G protein-coupled receptor-X2” [J. Dermatol. Sci. 112 (2023) 128–137] 他克莫司通过 MAS 相关 G 蛋白偶联受体-X2 对肥大细胞介导的过敏和炎症的双重作用》[J. Dermatol. Sci. 112 (2023) 128-137] 更正。

IF 4.6

Journal of dermatological science

Pub Date : 2024-09-01 DOI: 10.1016/j.jdermsci.2024.06.005

Xueshan Du , Delu Che , Bin Peng , Yi Zheng , Yong Hao , Tao Jia , Xinyue Zhang , Songmei Geng

引用次数: 0

Semaxanib, a VEGF inhibitor, suppresses melanogenesis by modulating CRTC3 independently of VEGF signaling 塞马沙尼（一种血管内皮生长因子抑制剂）通过调节 CRTC3（独立于血管内皮生长因子信号）抑制黑色素生成

IF 4.6

Journal of dermatological science

Pub Date : 2024-09-01 DOI: 10.1016/j.jdermsci.2024.07.004

HyeJi Kwon , Jeong Hyeon Lee , Jae Min Yoo , Huonggiang Nguyen , Hongchan An , Sung Eun Chang , Youngsup Song

Background

Dysregulation of melanogenesis contributes to the development of skin hyperpigmentation diseases, which poses a treatment challenge. Following the establishment of CRTC3 screening methods to explore small molecules inhibiting melanogenesis for the topical treatment of hyperpigmentation diseases, we identified a candidate molecule, semaxanib.

Objective

To explore the antimelanogenic effects of semaxanib, a vascular endothelial growth factor receptor (VEGFR) 2 inhibitor, for potential applications in hyperpigmentation management and to unravel the role of VEGF signaling in melanocyte biology by investigating mechanism of action of semaxanib.

Methods

Mouse-derived spontaneously immortalized melanocytes, B16F10, and normal human primary epidermal melanocytes cells were treated with semaxanib, and cellular responses were assessed using cell viability assays and melanin content measurements. Molecular mechanisms were investigated using transcriptional activity assays, reverse-transcription polymerase chain reaction, and immunoblotting analysis. In vivo studies were conducted using an epidermis-humanized transgenic mouse model and ex vivo human skin tissues.

Results

Semaxanib ameliorated melanin content in cultured melanocytes by downregulating the expression of melanogenesis-associated genes by suppressing the CRTC3/microphthalmia-associated transcription factors. Topical application of semaxanib reduced melanin accumulation in the ultraviolet B–stimulated ex vivo human epidermis and tail of K14-stem cell factor transgenic mice. Mechanistically, the antimelanogenic effect induced by semaxanib was associated with SIK2-CRTC3-MITF rather than VEGF signaling in melanocytes.

Conclusion

Semaxanib emerges as a promising candidate for the development of therapeutics for hyperpigmentation, potentially working independently of VEGF signaling in human melanocytes.

背景黑色素生成失调导致了皮肤色素沉着疾病的发生，这给治疗带来了挑战。目的探索血管内皮生长因子受体（VEGFR）2抑制剂semaxanib的抗黑色素生成作用，以发现其在色素沉着治疗中的潜在应用，并通过研究semaxanib的作用机制揭示VEGF信号在黑色素细胞生物学中的作用。方法用 semaxanib 处理小鼠自发永生的黑色素细胞 B16F10 和正常人原发性表皮黑色素细胞，并用细胞活力测定和黑色素含量测量评估细胞反应。利用转录活性测定、反转录聚合酶链反应和免疫印迹分析研究了分子机制。结果 semaxanib通过抑制CRTC3/微眼病相关转录因子，下调黑色素生成相关基因的表达，从而改善了培养黑色素细胞中黑色素的含量。局部应用semaxanib可减少紫外线B刺激的体外人体表皮和K14干细胞因子转基因小鼠尾部的黑色素积累。从机理上讲，semaxanib诱导的抗黑色素生成作用与黑素细胞中的SIK2-CRTC3-MITF而非血管内皮生长因子信号转导有关。

{"title":"Semaxanib, a VEGF inhibitor, suppresses melanogenesis by modulating CRTC3 independently of VEGF signaling","authors":"HyeJi Kwon , Jeong Hyeon Lee , Jae Min Yoo , Huonggiang Nguyen , Hongchan An , Sung Eun Chang , Youngsup Song","doi":"10.1016/j.jdermsci.2024.07.004","DOIUrl":"10.1016/j.jdermsci.2024.07.004","url":null,"abstract":"<div><h3>Background</h3><p>Dysregulation of melanogenesis contributes to the development of skin hyperpigmentation diseases, which poses a treatment challenge. Following the establishment of CRTC3 screening methods to explore small molecules inhibiting melanogenesis for the topical treatment of hyperpigmentation diseases, we identified a candidate molecule, semaxanib.</p></div><div><h3>Objective</h3><p>To explore the antimelanogenic effects of semaxanib, a vascular endothelial growth factor receptor (VEGFR) 2 inhibitor, for potential applications in hyperpigmentation management and to unravel the role of VEGF signaling in melanocyte biology by investigating mechanism of action of semaxanib.</p></div><div><h3>Methods</h3><p>Mouse-derived spontaneously immortalized melanocytes, B16F10, and normal human primary epidermal melanocytes cells were treated with semaxanib, and cellular responses were assessed using cell viability assays and melanin content measurements. Molecular mechanisms were investigated using transcriptional activity assays, reverse-transcription polymerase chain reaction, and immunoblotting analysis. <em>In vivo</em> studies were conducted using an epidermis-humanized transgenic mouse model and <em>ex vivo</em> human skin tissues.</p></div><div><h3>Results</h3><p>Semaxanib ameliorated melanin content in cultured melanocytes by downregulating the expression of melanogenesis-associated genes by suppressing the CRTC3/microphthalmia-associated transcription factors. Topical application of semaxanib reduced melanin accumulation in the ultraviolet B–stimulated <em>ex vivo</em> human epidermis and tail of K14-stem cell factor transgenic mice. Mechanistically, the antimelanogenic effect induced by semaxanib was associated with SIK2-CRTC3-MITF rather than VEGF signaling in melanocytes.</p></div><div><h3>Conclusion</h3><p>Semaxanib emerges as a promising candidate for the development of therapeutics for hyperpigmentation, potentially working independently of VEGF signaling in human melanocytes.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"115 3","pages":"Pages 121-129"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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