Journal of dermatological science最新文献_第3页

The decrease in peripheral blood basophils in a mouse model of IgE-induced inflammation involves their migration to lymph nodes 在 IgE 诱导的炎症小鼠模型中，外周血嗜碱性粒细胞的减少涉及它们向淋巴结的迁移。

IF 4.6

Journal of dermatological science

Pub Date : 2024-11-01 DOI: 10.1016/j.jdermsci.2024.09.004

Ni Ma , Izumi Kishimoto , Aki Tajima , Noriko Kume , Naotomo Kambe , Hideaki Tanizaki

Background

During the active phase of urticaria, a decrease in peripheral blood basophils, known as basopenia, is observed. We previously reported that basopenia occurs as a result of basophils migrating to the skin in a contact dermatitis model where a Th2 response is induced with oxazolone.

Objective

Although there is currently no established model for urticaria, given that urticaria is an IgE-mediated immediate-type allergic reaction, we aimed to determine whether an IgE-mediated model could reproduce the decrease in basophils in peripheral blood observed during the active phase of urticaria.

Methods

Mice were pretreated with 2,4,6-trinitrophenylhaptene (TNP)-specific IgE and basophil dynamics were examined following stimulation with TNP-ovalbumin. Mast cell-deficient WBB6F1-Kit^W/Kit^W-v mice were used to investigate the role of mast cells in this IgE-mediated model.

Results

Following stimulation, we observed immediate ear swelling and basopenia after 0.5 hours. However, the number of basophils observed in the skin lesions was low, while a higher number of basophils were observed in the antigen-draining lymph nodes (LN). In mast cell-deficient mice, no increase in basophils in the LN was observed, reflecting reduced antigen influx into the LN, but basophils remained in the skin.

Conclusions

In the IgE-mediated mouse model, basopenia was observed, which coincided with the induction of inflammation in the skin. The migration of basophils to the LN in this model suggests that the systemic immune system, including the LN, should be considered when exploring the pathogenesis of urticaria in humans.

背景：在荨麻疹的活动期，可观察到外周血嗜碱性粒细胞减少，即嗜碱性粒细胞减少症。我们以前曾报道过，在接触性皮炎模型中，嗜碱性粒细胞迁移到皮肤会导致嗜碱性粒细胞减少：尽管目前还没有荨麻疹的成熟模型，但鉴于荨麻疹是一种 IgE 介导的即时型过敏反应，我们旨在确定 IgE 介导的模型是否能重现荨麻疹活动期观察到的外周血嗜碱性粒细胞减少的现象：方法：用 2,4,6-三硝基苯基硫醇（TNP）特异性 IgE 对小鼠进行预处理，并在 TNP-ovalbumin 刺激后检测嗜碱性粒细胞的动态变化。使用肥大细胞缺陷的 WBB6F1-KitW/KitW-v 小鼠来研究肥大细胞在这种 IgE 介导的模型中的作用：结果：刺激后，我们观察到耳朵立即肿胀，并在 0.5 小时后出现嗜碱性粒细胞减少。然而，在皮肤病变中观察到的嗜碱性粒细胞数量较少，而在抗原引流淋巴结（LN）中观察到的嗜碱性粒细胞数量较多。在肥大细胞缺陷的小鼠中，淋巴结中的嗜碱性粒细胞没有增加，这反映了流入淋巴结的抗原减少，但皮肤中仍有嗜碱性粒细胞：结论：在 IgE 介导的小鼠模型中，观察到嗜碱性粒细胞减少，这与皮肤炎症的诱导相吻合。该模型中嗜碱性粒细胞向LN的迁移表明，在探索人类荨麻疹的发病机制时，应考虑包括LN在内的全身免疫系统。

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引用次数: 0

Downregulation of carnitine acetyltransferase by promoter hypermethylation regulates ultraviolet-induced matrix metalloproteinase-1 expression in human dermal fibroblasts 启动子超甲基化对肉碱乙酰转移酶的下调调节了紫外线诱导的人真皮成纤维细胞中基质金属蛋白酶-1的表达。

IF 4.6

Journal of dermatological science

Pub Date : 2024-11-01 DOI: 10.1016/j.jdermsci.2024.09.005

Min Ji Song , Min-Kyoung Kim , Chi-Hyun Park , Haesoo Kim , Si Hyung Lee , Dong Hun Lee , Jin Ho Chung

Background

Overexposure to ultraviolet (UV) radiation accelerates skin aging, resulting in wrinkle formation, reduced skin elasticity, and hyperpigmentation. UV irradiation induces increased matrix metalloproteinases (MMPs) that degrade collagen in the extracellular matrix. Skin aging is also accompanied by epigenetic alterations such as promoter methylation by DNA methyltransferases, leading to the activation or suppression of gene expression. Although carnitine acetyltransferase (CRAT) is implicated in aging, the effect of UV on the expression of CRAT and regulatory mechanisms of UV-induced MMP-1 expression remain unknown.

Objective

We investigated changes in CRAT expression upon UV irradiation and its effect on MMP-1 expression.

Methods

Primary human dermal fibroblasts were UV irradiated with either control or 5-AZA-dC. CRAT knockdown or overexpression was performed to investigate its effect on MMP-1 expression. The mRNA level was analyzed by quantitative real-time PCR, and protein level by western blotting.

Results

The expression of CRAT was decreased in UV-irradiated human skin in vivo and in human dermal fibroblasts in vitro. CRAT was downregulated upon UV irradiation by hypermethylation, and treatment with 5-Aza-2′-deoxycytidine, a DNA methyltransferase inhibitor, reversed UV-induced downregulation of CRAT. CRAT knockdown activated the JNK, ERK, and p38 MAPK signaling pathways, which increased MMP-1 expression. Stable overexpression of CRAT alleviated UV-induced MMP-1 induction.

Conclusion

CRAT downregulation caused by promoter hypermethylation may play an important role in UV-induced skin aging via upregulation of MMP-1 expression.

背景：过度暴露于紫外线（UV）辐射会加速皮肤老化，导致皱纹形成、皮肤弹性降低和色素沉着。紫外线照射会诱导基质金属蛋白酶（MMPs）增加，从而降解细胞外基质中的胶原蛋白。皮肤老化还伴随着表观遗传学的改变，如 DNA 甲基转移酶导致启动子甲基化，从而激活或抑制基因表达。虽然肉碱乙酰转移酶（CRAT）与衰老有关，但紫外线对 CRAT 表达的影响以及紫外线诱导 MMP-1 表达的调控机制仍不清楚：我们研究了紫外线照射时 CRAT 表达的变化及其对 MMP-1 表达的影响：方法：用对照组或 5-AZA-dC 对原代人真皮成纤维细胞进行紫外线照射。方法：用对照组或 5-AZA-dC 对原代人真皮成纤维细胞进行紫外线照射，敲除或过表达 CRAT，以研究其对 MMP-1 表达的影响。mRNA水平通过实时定量PCR分析，蛋白水平通过Western印迹分析：结果：CRAT在体内紫外线照射的人类皮肤和体外人类真皮成纤维细胞中的表达均下降。用 DNA 甲基转移酶抑制剂 5-Aza-2'-deoxycytidine 处理可逆转紫外线诱导的 CRAT 下调。CRAT 下调激活了 JNK、ERK 和 p38 MAPK 信号通路，从而增加了 MMP-1 的表达。稳定过表达 CRAT 可减轻紫外线诱导的 MMP-1 诱导：结论：启动子高甲基化导致的CRAT下调可能通过上调MMP-1的表达在紫外线诱导的皮肤老化中扮演重要角色。

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引用次数: 0

Type 2 cytokine-JAK1 signaling is involved in the development of dry skin-induced mechanical alloknesis. 2型细胞因子- jak1信号通路参与干性皮肤机械异位的发生。

IF 4.6

Journal of dermatological science

Pub Date : 2024-10-22 DOI: 10.1016/j.jdermsci.2024.10.002

Yui Toyosawa, Eriko Komiya, Takahide Kaneko, Yasushi Suga, Mitsutoshi Tominaga, Kenji Takamori

Background: Mechanical alloknesis (m-alloknesis) is itch hypersensitivity induced by normally innocuous stimuli. It is sometimes observed in dry skin based itch-related diseases such as atopic dermatitis (AD), and often triggers the vicious itch-scratch cycle. The acetone-ether and water (AEW) mouse model mimics dry skin-induced m-alloknesis, yet its underlying mechanism remains unclear. Janus kinase (JAK) inhibitors are used to treat AD, but their effects on m-alloknesis are not fully known.

Objective: To reveal the effects of various oral JAK inhibitors on m-alloknesis and their action points, using AEW model.

Methods: AEW model was prepared by treatment with a mixture of acetone-ether, and they were orally administrated a JAK1/2 inhibitor baricitinib, a selective JAK1 inhibitor abrocitinib, or a JAK2 selective inhibitor AZ960, and evaluated m-alloknesis score as the total number of scratching responses in 30 mechanical stimulations. To further elucidate the mechanism of action, IL-4, IL-13 or thymic stromal lymphopoietin (TSLP) or their neutralizing antibodies were also applied to mice. In addition, the levels of these cytokines in mouse skin were measured using multiple immunoassays.

Results: All of JAK inhibitors effectively reduced m-alloknesis, with abrocitinib demonstrating the most significant inhibition. The neutralizing antibodies against IL-4, IL-13, and TSLP inhibited m-alloknesis in AEW mice. Intradermal administration of IL-4, IL-13, or TSLP induced m-alloknesis, and abrocitinib effectively mitigated each cytokine-induced response. Highly sensitive assays detected IL-4, IL-13, IL-31 and TSLP in AEW-treated skin, with TSLP levels significantly increased.

Conclusion: Type 2 cytokine-JAK1 signaling is involved in the development of m-alloknesis in dry skin.

背景：机械异位是由通常无害的刺激引起的瘙痒过敏。它有时见于皮肤干燥性瘙痒相关疾病，如特应性皮炎（AD），并经常引发恶性瘙痒-抓伤循环。丙酮醚和水（AEW）小鼠模型模拟干皮肤诱导的m-异变，但其潜在机制尚不清楚。Janus kinase （JAK）抑制剂用于治疗AD，但其对m- allokesis的影响尚不完全清楚。目的：采用AEW模型，观察各种口服JAK抑制剂对m-异位化及其作用点的影响。方法：采用丙酮醚混合物治疗AEW模型，分别口服JAK1/2抑制剂baricitinib、JAK1选择性抑制剂abrocitinib或JAK2选择性抑制剂AZ960，并以30次机械刺激下挠性反应的总次数作为m-alloknesis评分。为了进一步阐明其作用机制，还将IL-4、IL-13或胸腺基质淋巴生成素（TSLP）或其中和抗体应用于小鼠。此外，这些细胞因子的水平在小鼠皮肤测量使用多种免疫分析。结果：所有JAK抑制剂均能有效降低m-异变，其中阿布替尼的抑制作用最显著。抗IL-4、IL-13和TSLP的中和抗体抑制AEW小鼠的m-异变。皮内给予IL-4、IL-13或TSLP诱导的m-异位，以及阿布昔替尼有效地减轻了每种细胞因子诱导的反应。高灵敏度检测方法检测了aew处理皮肤中IL-4、IL-13、IL-31和TSLP， TSLP水平显著升高。结论：2型细胞因子- jak1信号通路参与干性皮肤m-异位的发生。

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引用次数: 0

Staphylococcus epidermidis augments human β-defensin-3 synthesis through the transforming growth factor alpha-epidermal growth factor receptor cascade 表皮葡萄球菌通过转化生长因子α-表皮生长因子受体级联促进人类β-防御素-3的合成

IF 4.6

Journal of dermatological science

Pub Date : 2024-10-01 DOI: 10.1016/j.jdermsci.2024.08.003

Rie Ommori, Satoru Shinkuma, Hideo Asada

Background

Epidermal growth factor receptor inhibitors (EGFRIs) reduce β-defensin 3 (BD3) from keratinocytes stimulated by S. epidermidis, potentially leading to the development of acneiform rashes in patients undergoing EGFRIs treatment. However, the mechanism through which S. epidermidis induces BD3 via EGFR remains incompletely understood.

Objective

To elucidate the BD3 production pathway triggered by S. epidermidis.

Methods

To assess the impact of S. epidermidis on EGFR ligand expression, the levels of released EGFR ligands in the keratinocyte culture medium following S. epidermidis stimulation were quantified using ELISA. Subsequently, to confirm the synergistic effect of TGF-α and S. epidermidis, we administered S. epidermidis and TGF-α to the keratinocyte culture medium and measured the expression levels of BD3. In addition, we stimulated Toll-like receptor 2 (TLR2)-knockdown keratinocytes with S. epidermidis and measured the expression levels of TGF-α.

Results

While S. epidermidis did not induce EGF and HB-EGF, they increased TGF-α. The expression of BD3 was higher in keratinocytes stimulated by S. epidermidis in the presence of TGF-α, as compared to its absence. Moreover, both S. epidermidis- and TGF-α-induced BD3 were significantly suppressed by cetuximab. The expression levels of TGF-α induced by S. epidermidis were reduced in TLR2-knockdown keratinocytes

Conclusion

Our findings suggest that S. epidermidis induces the expression of TGF-α in keratinocytes through TLR2, which, in cooperation with TGF-α, stimulates the production of BD3.

背景：表皮生长因子受体抑制剂（EGFRIs）可减少表皮葡萄球菌刺激角质形成细胞产生的β-防御素3（BD3），从而可能导致接受EGFRIs治疗的患者出现痤疮样皮疹。然而，表皮葡萄球菌通过表皮生长因子受体诱导 BD3 的机制仍不完全清楚：阐明表皮葡萄球菌诱导 BD3 的产生途径：为了评估表皮葡萄球菌对表皮生长因子受体配体表达的影响，使用 ELISA 定量表皮葡萄球菌刺激后角质形成细胞培养液中释放的表皮生长因子受体配体的水平。随后，为了证实 TGF-α 和表皮葡萄球菌的协同作用，我们在角质形成细胞培养液中加入了表皮葡萄球菌和 TGF-α，并测定了 BD3 的表达水平。此外，我们还用表皮葡萄球菌刺激了Toll样受体2（TLR2）敲除的角质形成细胞，并测量了TGF-α的表达水平：结果：表皮葡萄球菌没有诱导 EGF 和 HB-EGF，但增加了 TGF-α。在有 TGF-α 的情况下，表皮葡萄球菌刺激的角质形成细胞中 BD3 的表达量比没有 TGF-α 时要高。此外，西妥昔单抗还能显著抑制表皮葡萄球菌和 TGF-α 诱导的 BD3。表皮葡萄球菌诱导的 TGF-α 的表达水平在 TLR2-敲除的角质形成细胞中有所降低结论：我们的研究结果表明，表皮葡萄球菌通过 TLR2 诱导角质形成细胞中 TGF-α 的表达，TLR2 与 TGF-α 合作刺激 BD3 的产生。

{"title":"Staphylococcus epidermidis augments human β-defensin-3 synthesis through the transforming growth factor alpha-epidermal growth factor receptor cascade","authors":"Rie Ommori, Satoru Shinkuma, Hideo Asada","doi":"10.1016/j.jdermsci.2024.08.003","DOIUrl":"10.1016/j.jdermsci.2024.08.003","url":null,"abstract":"<div><h3>Background</h3><div>Epidermal growth factor receptor inhibitors (EGFRIs) reduce β-defensin 3 (BD3) from keratinocytes stimulated by <em>S. epidermidis</em>, potentially leading to the development of acneiform rashes in patients undergoing EGFRIs treatment. However, the mechanism through which <em>S. epidermidis</em> induces BD3 via EGFR remains incompletely understood.</div></div><div><h3>Objective</h3><div>To elucidate the BD3 production pathway triggered by <em>S. epidermidis</em>.</div></div><div><h3>Methods</h3><div>To assess the impact of <em>S. epidermidis</em> on EGFR ligand expression, the levels of released EGFR ligands in the keratinocyte culture medium following <em>S. epidermidis</em> stimulation were quantified using ELISA. Subsequently, to confirm the synergistic effect of TGF-α and <em>S. epidermidis</em>, we administered <em>S. epidermidis</em> and TGF-α to the keratinocyte culture medium and measured the expression levels of BD3. In addition, we stimulated Toll-like receptor 2 (TLR2)-knockdown keratinocytes with <em>S. epidermidis</em> and measured the expression levels of TGF-α.</div></div><div><h3>Results</h3><div>While <em>S. epidermidis</em> did not induce EGF and HB-EGF, they increased TGF-α. The expression of BD3 was higher in keratinocytes stimulated by <em>S. epidermidis</em> in the presence of TGF-α, as compared to its absence. Moreover, both <em>S. epidermidis</em>- and TGF-α-induced BD3 were significantly suppressed by cetuximab. The expression levels of TGF-α induced by <em>S. epidermidis</em> were reduced in TLR2-knockdown keratinocytes</div></div><div><h3>Conclusion</h3><div>Our findings suggest that <em>S. epidermidis</em> induces the expression of TGF-α in keratinocytes through TLR2, which, in cooperation with TGF-α, stimulates the production of BD3.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"116 1","pages":"Pages 34-40"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304944","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}

引用次数: 0

Dermal fibroblasts retain site-specific transcriptomic identity in keloids 皮肤成纤维细胞在瘢痕疙瘩中保留了特定部位的转录组特征。

IF 4.6

Journal of dermatological science

Pub Date : 2024-10-01 DOI: 10.1016/j.jdermsci.2024.08.002

Pingping Lin , Daoning Zhang , Jie Tian , Binbin Lai , Yu Yang , Yicen Yan , Shenxi Zhang , Guohong Zhang , Hang Li

Background

Human skin displays extensive spatial heterogeneity and maintains distinct positional identity. However, the impact of disease processes on these site-specific differences remains poorly understood, especially in keloid, a skin disorder characterized by pronounced spatial heterogeneity.

Objective

This study aimed to assess whether the spatial heterogeneity and positional identity observed in different anatomic sites persist in keloids.

Methods

Transcriptome sequencing was conducted on 139 keloid dermal tissues and 19 keloid fibroblast samples spanning seven distinct anatomic sites to identify the spatial transcriptomic heterogeneity. In addition, single-cell RNA sequencing data were utilized to elucidate the contributions of various cell types to the maintenance of positional identity.

Results

Keloid dermal tissues from diverse sites were categorized into three anatomic groupings: trunk and extremity, ear, and mandible regions. Enrichment analysis of differentially expressed genes unveiled that keloids across distinct regions retained unique anatomically-related gene expression profiles, reminiscent of those observed in normal skin. Notably, regional disparities consistently prevailed and surpassed inter-donor variations. Single-cell RNA sequencing further revealed that mesenchymal cells, particularly fibroblasts, made major contributions to positional identity in keloids. Moreover, gene expression profiles in primary keloid fibroblasts demonstrated a remarkable persistence of positional identity, enduring even after prolonged in vitro propagation.

Conclusion

Taken together, these findings imply that keloids remain positional identity and developmental imprinting characteristic of normal skin. Fibroblasts predominantly contribute to the spatial heterogeneity observed in keloids.

背景：人类皮肤具有广泛的空间异质性，并保持着独特的位置特性。然而，人们对疾病过程对这些特定部位差异的影响仍然知之甚少，尤其是对瘢痕疙瘩这种以明显的空间异质性为特征的皮肤疾病：本研究旨在评估在不同解剖部位观察到的空间异质性和位置同一性在瘢痕疙瘩中是否持续存在：方法：对139个瘢痕疙瘩真皮组织和19个瘢痕疙瘩成纤维细胞样本进行转录组测序，横跨7个不同的解剖部位，以确定空间转录组异质性。此外，还利用单细胞 RNA 测序数据来阐明各种细胞类型对位置特性维持的贡献：结果：来自不同部位的瘢痕疙瘩真皮组织被分为三个解剖组：躯干和四肢、耳朵和下颌区域。差异表达基因的富集分析表明，不同区域的瘢痕疙瘩保留了独特的解剖相关基因表达谱，与正常皮肤中观察到的基因表达谱相似。值得注意的是，区域差异始终占主导地位，并超过了供体间差异。单细胞 RNA 测序进一步显示，间充质细胞，尤其是成纤维细胞，对瘢痕疙瘩的位置特征做出了重要贡献。此外，原发性瘢痕疙瘩成纤维细胞的基因表达图谱显示，位置特征具有显著的持久性，即使在体外长期繁殖后仍能保持：综上所述，这些研究结果表明，瘢痕疙瘩仍具有正常皮肤的位置特征和发育印记。成纤维细胞是瘢痕疙瘩空间异质性的主要成因。

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引用次数: 0

Dysbiosis-activated IL-17-producing T cells promote skin immunopathological progression in mice deficient of the Notch ligand Jag1 in keratinocytes 在角质形成细胞中缺乏 Notch 配体 Jag1 的小鼠体内，菌群失调激活的产生 IL-17 的 T 细胞会促进皮肤免疫病理学的发展。

IF 4.6

Journal of dermatological science

Pub Date : 2024-10-01 DOI: 10.1016/j.jdermsci.2024.09.001

Eun Hyeon Song , Juan Garcia Jr. , Na Xiong

Background

The Notch signaling pathway is an evolutionarily conserved regulatory cascade critical in skin development and homeostasis. Mice deficient of Notch signaling molecules have impaired skin and hair follicle development associated with local tissue inflammation. However, mechanisms underlying skin inflammation and pathology resulting from defective Notch signals are not well understood.

Objective

To dissect molecular and cellular mechanisms underlying development of skin immunopathology in mice defective of the Notch ligand Jagged-1 (Jag1).

Methods

We assessed involvement of microbiota and immune cell subsets in skin pathogenic symptoms in Foxn1^CreJag1^fl/fl mice that were deficient of Jag1 in keratinocytes. We also used RNA-seq and 16S rRNA gene-seq analyses to identify molecular factors and bacterial species contributing to skin pathologic symptoms in Foxn1^CreJag1^fl/fl mice.

Results

Compared to Jag1-sufficient littermate control mice, Foxn1^CreJag1^fl/fl mice had specific expansion of IL-17a-producing T cells accompanying follicular and epidermal hyperkeratosis and cyst formation while antibody blockage of IL-17a reduced the skin pathology. RNA-sequencing and 16S rRNA gene-sequencing analyses revealed dysregulated immune responses and altered microbiota compositions in the skin of Foxn1^CreJag1^fl/fl mice. Antibiotic treatment completely prevented over-activation of IL-17a-producing T cells and alleviated skin pathology in Foxn1^CreJag1^fl/fl mice.

Conclusion

Dysbiosis-induced over-activation of IL-17a-producing T cells is critically involved in development of skin pathology in Foxn1^CreJag1^fl/fl mice, establishing Foxn1^CreJag1^fl/fl mice as a useful model to study pathogenesis and therapeutic targets in microbiota-IL-17-mediated skin inflammatory diseases such as hidradenitis suppurativa (HS) and psoriasis.

背景：Notch 信号通路是一种进化保守的调控级联，对皮肤发育和稳态至关重要。缺乏 Notch 信号分子的小鼠皮肤和毛囊发育受损，并伴有局部组织炎症。然而，Notch 信号缺陷导致的皮肤炎症和病理机制尚不十分清楚：目的：研究 Notch 配体 Jagged-1 (Jag1) 缺陷小鼠皮肤免疫病理学发展的分子和细胞机制：我们评估了Foxn1CreJag1fl/fl小鼠皮肤致病症状中微生物群和免疫细胞亚群的参与情况，这些小鼠的角质形成细胞中缺乏Jag1。我们还利用RNA-seq和16S rRNA基因-seq分析确定了导致Foxn1CreJag1fl/fl小鼠皮肤病理症状的分子因素和细菌种类：结果：与Jag1不足的同窝对照小鼠相比，Foxn1CreJag1fl/fl小鼠产生IL-17a的T细胞特异性扩增，并伴有滤泡和表皮角化过度和囊肿形成，而抗体阻断IL-17a可减轻皮肤病理变化。RNA 序列和 16S rRNA 基因序列分析表明，Foxn1CreJag1fl/fl 小鼠皮肤的免疫反应失调，微生物群组成发生改变。抗生素治疗可完全阻止产生 IL-17a 的 T 细胞过度激活，并减轻 Foxn1CreJag1fl/fl 小鼠的皮肤病理变化：Foxn1CreJag1fl/fl小鼠皮肤病理学的发展关键在于菌群失调诱导的产生IL-17a的T细胞过度激活，因此Foxn1CreJag1fl/fl小鼠是研究微生物-IL-17介导的皮肤炎症性疾病（如化脓性扁桃体炎（HS）和银屑病）的发病机制和治疗靶点的有用模型。

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引用次数: 0

Possible facilitating role of IL-17A on IL-23 production in keratinocytes in psoriatic lesions IL-17A 可能对银屑病皮损中角质细胞产生 IL-23 起到促进作用。

IF 4.6

Journal of dermatological science

Pub Date : 2024-10-01 DOI: 10.1016/j.jdermsci.2024.09.002

Akimasa Adachi , Tetsuya Honda , Nobuhiro Kusuba , Fuuka Minami , Satoshi Nakamizo , Kenji Kabashima

引用次数: 0

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