Journal of dermatological science最新文献

英文中文

A modified Sobel filter-based automated numerical algorithm enables immediate trichoscopic assessment of hair diameter diversity in male and female pattern hair loss 一种改进的基于索贝尔过滤器的自动数值算法，可以立即对男性和女性脱发的头发直径多样性进行三分镜评估。

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/j.jdermsci.2023.11.004

Masaya Takagi, Misaki Kinoshita-Ise, Masahiro Fukuyama, Soichiro Aoki, Saori Nishikawa, Mami Miyoshi, Takaki Sugimoto, Masako Yamazaki, Masashi Ogo, Manabu Ohyama

引用次数: 0

Editor's Choice 编辑推荐

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/S0923-1811(24)00006-9

引用次数: 0

High migratory activity of dermal sheath cup cells associated with the clinical efficacy of autologous cell-based therapy for pattern hair loss 真皮鞘杯细胞的高迁移活性与自体细胞疗法治疗脱发的临床疗效有关

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/j.jdermsci.2023.11.003

Yumiko Ishimatsu-Tsuji , Shiro Niiyama , Ryokichi Irisawa , Kazutoshi Harada , Jiro Kishimoto , Ryoji Tsuboi

Background

Autologous cell-based therapy using dermal sheath cup (DSC) cells was reported as a new treatment for male and female pattern hair loss. However, the mechanisms underlying its action remain unclear.

Objective

We investigated the mechanisms underlying the efficacy of DSC cells in cell-based therapy.

Methods

We conducted multivariate analysis to categorize individuals based on treatment response as responders and non-responders. The differentially expressed genes in DSC cells from the two groups were evaluated using bulk transcriptome, quantitative polymerase chain reaction, and single-cell transcriptome analyses. We performed live cell imaging combined with immunostaining to characterize the DSC subpopulation associated with responders.

Results

We identified nine and three genes as high efficacy (HE) and low efficacy (LE) marker genes, respectively. The HE subpopulations were enriched for cell migration-related genes in single-cell analysis. In contrast, the LE subpopulation was enriched for basement membrane and vasculature-related genes. Moreover, DSC cells in culture were immunocytochemically and morphologically heterogeneous, expressing characteristic factors. Furthermore, live cell imaging showed that DSC cells expressing integrin subunit alpha 6 (ITGA6), an HE subpopulation gene, had markedly higher mobility than those expressing the LE subpopulation genes collagen type IV or CD36.

Conclusions

ITGA6-positive DSC cells, with superior migratory activity, may contribute to cell-based therapy by promoting cell migration into nearby hair follicles.

背景据报道，使用真皮鞘杯（DSC）细胞的自体细胞疗法是治疗男性和女性脱发的一种新疗法。方法我们进行了多变量分析，根据治疗反应将个体分为有反应者和无反应者。我们使用大量转录组、定量聚合酶链反应和单细胞转录组分析评估了两组 DSC 细胞中的差异表达基因。我们进行了活细胞成像并结合免疫染色，以确定与应答者相关的 DSC 亚群的特征。结果我们分别确定了 9 个和 3 个基因作为高效（HE）和低效（LE）标记基因。在单细胞分析中，HE 亚群富含细胞迁移相关基因。相比之下，LE 亚群富含基底膜和血管相关基因。此外，培养中的 DSC 细胞在免疫细胞化学和形态上具有异质性，表达特征性因子。此外，活细胞成像显示，表达整合素亚单位α6（ITGA6）（一种 HE 亚群基因）的 DSC 细胞比表达 LE 亚群基因Ⅳ型胶原蛋白或 CD36 的细胞具有明显更高的迁移性。

{"title":"High migratory activity of dermal sheath cup cells associated with the clinical efficacy of autologous cell-based therapy for pattern hair loss","authors":"Yumiko Ishimatsu-Tsuji , Shiro Niiyama , Ryokichi Irisawa , Kazutoshi Harada , Jiro Kishimoto , Ryoji Tsuboi","doi":"10.1016/j.jdermsci.2023.11.003","DOIUrl":"10.1016/j.jdermsci.2023.11.003","url":null,"abstract":"<div><h3>Background</h3><p>Autologous cell-based therapy using dermal sheath cup (DSC) cells was reported as a new treatment for male and female pattern hair loss. However, the mechanisms underlying its action remain unclear.</p></div><div><h3>Objective</h3><p>We investigated the mechanisms underlying the efficacy of DSC cells in cell-based therapy.</p></div><div><h3>Methods</h3><p>We conducted multivariate analysis to categorize individuals based on treatment response as responders and non-responders. The differentially expressed genes in DSC cells from the two groups were evaluated using bulk transcriptome, quantitative polymerase chain reaction, and single-cell transcriptome analyses. We performed live cell imaging combined with immunostaining to characterize the DSC subpopulation associated with responders.</p></div><div><h3>Results</h3><p>We identified nine and three genes as high efficacy (HE) and low efficacy (LE) marker genes, respectively. The HE subpopulations were enriched for cell migration-related genes in single-cell analysis. In contrast, the LE subpopulation was enriched for basement membrane and vasculature-related genes. Moreover, DSC cells in culture were immunocytochemically and morphologically heterogeneous, expressing characteristic factors. Furthermore, live cell imaging showed that DSC cells expressing integrin subunit alpha 6 (ITGA6), an HE subpopulation gene, had markedly higher mobility than those expressing the LE subpopulation genes collagen type IV or CD36.</p></div><div><h3>Conclusions</h3><p>ITGA6-positive DSC cells, with superior migratory activity, may contribute to cell-based therapy by promoting cell migration into nearby hair follicles.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181123002414/pdfft?md5=edfa610e798cd3f1b2fb6eed9771d813&pid=1-s2.0-S0923181123002414-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135615370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High glucose environment induces NEDD4 deficiency that impairs angiogenesis and diabetic wound healing 高糖环境诱导NEDD4缺乏，从而损害血管生成和糖尿病伤口愈合。

IF 4.6

Journal of dermatological science

Pub Date : 2023-12-01 DOI: 10.1016/j.jdermsci.2023.09.007

Yu Guo, Yongjie Wang, Haiwei Liu, Xulei Jiang, Shaorong Lei

Background

Healing of diabetic wounds, characterized by impaired angiogenesis, remains a clinical challenge. E3 ligase have been identified as potential therapeutic targets of wound healing.

Objective

We assessed the role of E3 ligase NEDD4 in the context of angiogenesis and diabetic wound healing.

Methods

The mRNA expression levels of NEDD4, TSP1 and VEGF were determined by real-time PCR. Western blotting was used to evaluate the protein expression of NEDD4, TSP1 and VEGF. The ubiquitination of TSP1 was evaluated by immunoprecipitation. MTT assay, wound healing assay and tube formation assay were performed to assess the proliferation, migration and angiogenic functions of endothelial cells. The epigenetic modification in the promoter of NEDD4 was confirmed using BSP assay and ChIP-qPCR assay. The role of NEDD4 in wound healing was further verified in diabetic mouse model.

Results

NEDD4 promotes proliferation, migration and tube formation of endothelial cells. It binds to and ubiquitinates TSP1, which lead to TSP1 degradation and thus increased VEGF expression. The inhibitory effect of NEDD4 silencing on the angiogenesis ability of endothelial cells can be restored by TSP1 knockdown. NEDD4 is reduced in diabetic patients, which may due to hypermethylation of NEDD4 promoter mediated via DNMT1 under high glucose condition. Furthermore, inhibition of NEDD4 represses wound healing in diabetic mouse model.

Conclusion

NEDD4 might promote angiogenesis and wound healing by inhibiting TSP1 via ubiquitination in diabetic patients.

背景：以血管生成受损为特征的糖尿病伤口的愈合仍然是一个临床挑战。E3连接酶已被确定为伤口愈合的潜在治疗靶点。目的：我们评估了E3连接酶NEDD4在血管生成和糖尿病伤口愈合中的作用。方法：采用实时聚合酶链反应检测NEDD4、TSP1和VEGF的mRNA表达水平。采用蛋白质印迹法检测NEDD4、TSP1和VEGF的蛋白表达。TSP1的泛素化通过免疫沉淀进行评估。MTT法、创伤愈合法和成管法检测内皮细胞的增殖、迁移和血管生成功能。使用BSP分析和ChIP-qPCR分析证实了NEDD4启动子的表观遗传学修饰。在糖尿病小鼠模型中进一步验证了NEDD4在伤口愈合中的作用。结果：NEDD4能促进内皮细胞的增殖、迁移和管形成。它与TSP1结合并泛素化，从而导致TSP1降解，从而增加VEGF的表达。NEDD4沉默对内皮细胞血管生成能力的抑制作用可以通过敲低TSP1来恢复。糖尿病患者的NEDD4减少，这可能是由于在高糖条件下通过DNMT1介导的NEDD4-启动子的高甲基化。此外，在糖尿病小鼠模型中，NEDD4的抑制抑制伤口愈合。结论：NEDD4可能通过泛素化抑制TSP1，从而促进糖尿病患者血管生成和伤口愈合。

{"title":"High glucose environment induces NEDD4 deficiency that impairs angiogenesis and diabetic wound healing","authors":"Yu Guo, Yongjie Wang, Haiwei Liu, Xulei Jiang, Shaorong Lei","doi":"10.1016/j.jdermsci.2023.09.007","DOIUrl":"10.1016/j.jdermsci.2023.09.007","url":null,"abstract":"<div><h3>Background</h3><p>Healing of diabetic wounds, characterized by impaired angiogenesis<span>, remains a clinical challenge. E3 ligase have been identified as potential therapeutic targets of wound healing.</span></p></div><div><h3>Objective</h3><p>We assessed the role of E3 ligase NEDD4 in the context of angiogenesis and diabetic wound healing.</p></div><div><h3>Methods</h3><p><span>The mRNA expression levels of NEDD4, TSP1<span><span> and VEGF were determined by real-time PCR. Western blotting was used to evaluate the </span>protein expression of NEDD4, TSP1 and VEGF. The </span></span>ubiquitination<span><span> of TSP1 was evaluated by immunoprecipitation. </span>MTT assay<span><span>, wound healing assay and tube formation assay were performed to assess the proliferation, migration and angiogenic functions of endothelial cells. The </span>epigenetic modification in the promoter of NEDD4 was confirmed using BSP assay and ChIP-qPCR assay. The role of NEDD4 in wound healing was further verified in diabetic mouse model.</span></span></p></div><div><h3>Results</h3><p>NEDD4 promotes proliferation, migration and tube formation of endothelial cells. It binds to and ubiquitinates TSP1, which lead to TSP1 degradation and thus increased VEGF expression. The inhibitory effect of NEDD4 silencing on the angiogenesis ability of endothelial cells can be restored by TSP1 knockdown. NEDD4 is reduced in diabetic patients, which may due to hypermethylation of NEDD4 promoter mediated via DNMT1 under high glucose condition. Furthermore, inhibition of NEDD4 represses wound healing in diabetic mouse model.</p></div><div><h3>Conclusion</h3><p>NEDD4 might promote angiogenesis and wound healing by inhibiting TSP1 via ubiquitination in diabetic patients.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490526","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

Alopecia areata: What’s new in the epidemiology, comorbidities, and pathogenesis? 斑秃：流行病学、合并症和发病机制有什么新进展？

IF 4.6

Journal of dermatological science

Pub Date : 2023-12-01 DOI: 10.1016/j.jdermsci.2023.09.008

Teruki Dainichi , Masashi Iwata , Yo Kaku

Background

Alopecia areata (AA) is a common, acquired, and nonscarring type of hair loss that affects people of every generation and is intractable in severe and relapsing cases. Patients with AA, especially those with greater scalp involvement, have poor health-related quality-of-life scores. Purpose: Following our previous review article in the April 2017 issue of the Journal of Dermatological Science, we aim to provide a pair of review articles on recent progress in multidisciplinary approaches to AA. Main findings: We found more than 1800 publications on AA from July 2016 to December 2022. Conclusions: In this review, we focused on the latest information on the epidemiology, comorbidities, and pathogenesis of AA.

背景：斑秃（AA）是一种常见的、获得性的、非持续性的脱发，影响每一代人，在严重和复发的病例中很难治愈。AA患者，尤其是头皮受累较多的患者，健康相关生活质量评分较差。目的：继我们在《皮肤病学杂志》2017年4月号上发表的上一篇综述文章之后，我们的目标是提供两篇关于AA多学科方法最新进展的综述文章。主要发现：从2016年7月到2022年12月，我们发现了1800多篇关于AA的出版物。结论：在这篇综述中，我们重点关注流行病学的最新信息，合并症和AA的发病机制。

引用次数: 0

METTL14-mediated N6-methyladenosine modification of Col17a1/Itgα6/Itgβ4 governs epidermal homeostasis mettl14介导的Col17a1/Itgα6/Itgβ4的n6 -甲基腺苷修饰控制表皮稳态。

IF 4.6

Journal of dermatological science

Pub Date : 2023-12-01 DOI: 10.1016/j.jdermsci.2023.10.005

Renpeng Zhou , Qirui Wang , Siyi Zeng, Yimin Liang, Danru Wang

Background

N6-methyladenosine (m⁶A) is the most abundant and reversible modification occurring in eukaryotic mRNAs, however, its functions in mammalian epidermal development are still not fully elucidated.

Objective

To explore the role of METTL14 (Methyltransferase like 14), one of the m⁶A methyltransferases, in maintaining epidermal homeostasis.

Methods

We constructed mice with Mettl14-inactivation in the epidermal basal cells. The phenotype was explored by H&E staining and immunofluorescence staining. To explore the underlying mechanisms, we performed RNA-seq, Ribosome profiling and MeRIP-seq on wild-type and Mettl14-inactivation epidermal keratinocytes. Moreover, HaCaT cells were used for in vitro validation.

Results

Inactivation of Mettl14 in murine epidermis led to transient thicker epidermis and exhaustion of the epidermal stem cell pool. Interestingly, we found that the mRNA of type XVII collagen (Col17a1), integrin β4 (Itgβ4) and α6 (Itgα6) had m⁶A modifications, and the proteins expression were decreased in Mettl14-inactivated epidermis. Furthermore, in epidermis-specific Mettl4-inactivated mice, the epidermis was detached from the dermis and presented a phenotype similar to junctional epidermolysis bullosa (JEB), which may result from hemidesmosomes damage (decrease of COL17A1, ITGB4 and ITGA6). Knockdown of Mettl14 in HaCaT cells impaired the self-renewal and decreased the protein level of COL17A1, ITGB4 and ITGA6 and Itgβ4 knockdown inhibited colony formation.

Conclusion

Our study highlighted the role of METTL14 in the maintenance of epidermal homeostasis and identified its critical role through m⁶A-mediated translational inhibition of Col17a1, Itgβ4 and Itgα6. Our study suggested that METTL14 may be a potential therapeutic target for the treatment of hemidesmosomes-deficient diseases, such as JEB.

背景:n6 -甲基腺苷(n6 - methylladenosine, m6A)是真核生物mrna中最丰富、最可逆的修饰，但其在哺乳动物表皮发育中的功能尚未完全阐明。目的:探讨m6A甲基转移酶之一METTL14 (Methyltransferase like 14)在维持表皮稳态中的作用。方法:构建表皮基底细胞mettl14失活小鼠。H&E染色和免疫荧光染色探讨表型。为了探索潜在的机制，我们对野生型和mettl14失活的表皮角质形成细胞进行了RNA-seq、核糖体分析和MeRIP-seq。此外，HaCaT细胞用于体外验证。结果:小鼠表皮中Mettl14的失活导致表皮短暂增厚和表皮干细胞池耗竭。有趣的是，我们发现XVII型胶原蛋白(Col17a1)、整合素β4 (Itgβ4)和α6 (Itgα6)的mRNA存在m6A修饰，并且在mettl14失活的表皮中表达减少。此外，在表皮特异性mettl4灭活小鼠中，表皮与真皮分离，呈现类似于交界性大泡表皮松解症(JEB)的表型，这可能是由半半粒损伤(COL17A1、ITGB4和ITGA6减少)引起的。敲低Mettl14抑制HaCaT细胞自我更新，降低COL17A1、ITGB4和ITGA6蛋白水平，敲低Itgβ4抑制集落形成。结论:我们的研究强调了METTL14在维持表皮稳态中的作用，并通过m6a介导的Col17a1、Itgβ4和Itgα6的翻译抑制确定了其关键作用。我们的研究表明，METTL14可能是治疗半染色体缺陷疾病(如JEB)的潜在治疗靶点。

{"title":"METTL14-mediated N6-methyladenosine modification of Col17a1/Itgα6/Itgβ4 governs epidermal homeostasis","authors":"Renpeng Zhou , Qirui Wang , Siyi Zeng, Yimin Liang, Danru Wang","doi":"10.1016/j.jdermsci.2023.10.005","DOIUrl":"10.1016/j.jdermsci.2023.10.005","url":null,"abstract":"<div><h3>Background</h3><p>N6-methyladenosine (m<sup>6</sup>A) is the most abundant and reversible modification occurring in eukaryotic mRNAs, however, its functions in mammalian epidermal development are still not fully elucidated.</p></div><div><h3>Objective</h3><p>To explore the role of METTL14 (Methyltransferase like 14), one of the m<sup>6</sup><span>A methyltransferases, in maintaining epidermal homeostasis.</span></p></div><div><h3>Methods</h3><p>We constructed mice with <em>Mettl14</em><span><span>-inactivation in the epidermal basal cells. The phenotype was explored by H&E staining and </span>immunofluorescence staining. To explore the underlying mechanisms, we performed RNA-seq, Ribosome profiling and MeRIP-seq on wild-type and </span><em>Mettl14</em><span><span>-inactivation epidermal keratinocytes. Moreover, </span>HaCaT cells were used for </span><em>in vitro</em> validation.</p></div><div><h3>Results</h3><p>Inactivation of <em>Mettl14</em><span><span><span> in murine epidermis led to transient thicker epidermis and exhaustion of the epidermal stem cell pool. Interestingly, we found that the mRNA of </span>type XVII collagen (Col17a1), </span>integrin β4 (Itgβ4) and α6 (Itgα6) had m</span><sup>6</sup><span>A modifications, and the proteins expression were decreased in </span><em>Mettl14</em>-inactivated epidermis. Furthermore, in epidermis-specific <em>Mettl4</em><span><span>-inactivated mice, the epidermis was detached from the dermis and presented a phenotype similar to </span>junctional epidermolysis bullosa<span> (JEB), which may result from hemidesmosomes damage (decrease of COL17A1, ITGB4 and ITGA6). Knockdown of </span></span><em>Mettl14</em> in HaCaT cells impaired the self-renewal and decreased the protein level of COL17A1, ITGB4 and ITGA6 and <em>Itgβ4</em> knockdown inhibited colony formation.</p></div><div><h3>Conclusion</h3><p>Our study highlighted the role of METTL14 in the maintenance of epidermal homeostasis and identified its critical role through m<sup>6</sup><span>A-mediated translational inhibition of Col17a1, Itgβ4 and Itgα6. Our study suggested that METTL14 may be a potential therapeutic target for the treatment of hemidesmosomes-deficient diseases, such as JEB.</span></p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89721336","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

Bath-psoralen plus UVA therapy changes inflammatory proteomic signatures for systemic effects beyond the skin 沐浴补骨脂素加UVA疗法改变炎症蛋白质组学特征，对皮肤以外的系统性影响。

IF 4.6

Journal of dermatological science

Pub Date : 2023-12-01 DOI: 10.1016/j.jdermsci.2023.09.004

Yoshifumi Kanayama, Kyoko Ikumi, Mai Sakurai, Yuki Enomoto, Emi Nishida, Aya Yamamoto, Akimichi Morita

引用次数: 0

Two novel MBTPS2 missense mutations impairing S2P proteolytic activity lead to IFAP syndrome with new phenotypic anomalies 损害S2P蛋白水解活性的两个新的MBTPS2错义突变导致具有新表型异常的IFAP综合征。

IF 4.6

Journal of dermatological science

Pub Date : 2023-12-01 DOI: 10.1016/j.jdermsci.2023.10.004

Natarin Caengprasath , Mathilde Nizon , Ratchathorn Panchaprateep , Benjamin Cogne , Silvestre Cuinat , Hélène Auburt , Nathalie Jonca , Thantrira Porntaveetus , Vorasuk Shotelersuk

引用次数: 0

Editor's Choice 编辑推荐

IF 4.6

Journal of dermatological science

Pub Date : 2023-12-01 DOI: 10.1016/S0923-1811(23)00262-1

引用次数: 0

Dual effect of tacrolimus on mast cell–mediated allergy and inflammation through Mas-related G protein-coupled receptor X2 他克莫司通过肥大细胞相关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。

IF 4.6

Journal of dermatological science

Pub Date : 2023-12-01 DOI: 10.1016/j.jdermsci.2023.10.003

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

Background

Topical tacrolimus, although widely used in the treatment of dermatoses, presents with an immediate irritation on initial application resembling a pseudo-allergic reaction. Mas-related G protein-coupled receptor X2 (MRGPRX2) in mast cells (MCs) mediates drug-induced pseudo-allergic reaction and immunoglobulin E (IgE)-independent pruritis in chronic skin diseases. However, the immunosuppression mechanism of tacrolimus on MCs via MRGPRX2 has not been reported.

Objective

To investigate the role of MRGPRX2 and the mechanism of action of tacrolimus on its short-term and long-term applications.

Methods

Wild-type mice, Kit^W-sh/W-sh mice, and MrgprB2-deficient (MUT) mice were used to study the effect of tacrolimus on in vivo anaphylaxis model. LAD2 cells and MRGPRX2-knockdown LAD2 cells were specifically used to derive the associated mechanism of the tacrolimus effect.

Results

Short-term application of tacrolimus triggers IgE-independent activation of MCs via MRGPRX2/B2 in both in vivo and in vitro experiments. Tacrolimus binds to MRGPRX2, which was verified by fluorescently labeled tacrolimus in cells. On long-term treatment with tacrolimus, the initial allergic reaction fades away corresponding with the downregulation of MRGPRX2, which leads to decreased release of inflammatory cytokines (P < 0.05 to P < 0.001).

Conclusion

Short-term treatment with tacrolimus induces pseudo-allergic reaction via MRGPRX2/B2 in MCs, whereas long-term treatment downregulates expression of MRGPRX2/B2, which may contribute to its potent immunosuppressive effect in the treatment of various skin diseases.

背景:局部他克莫司虽然广泛用于治疗皮肤病，但在初次应用时表现出立即刺激，类似于伪过敏反应。肥大细胞(MCs)中mass相关G蛋白偶联受体X2 (MRGPRX2)介导慢性皮肤病中药物诱导的假性过敏反应和免疫球蛋白E (IgE)非依赖性瘙痒。然而，他克莫司通过MRGPRX2对MCs的免疫抑制机制尚未见报道。目的:探讨MRGPRX2的作用及他克莫司对其短期和长期应用的作用机制。方法:采用野生型小鼠、KitW-sh/W-sh小鼠和mrgprb2缺陷(MUT)小鼠，研究他克莫司对体内过敏反应模型的影响。LAD2细胞和mrgprx2敲低的LAD2细胞被专门用来推导他克莫司效应的相关机制。结果:在体内和体外实验中，短期应用他克莫司可通过MRGPRX2/B2触发MCs的ige非依赖性激活。他克莫司与MRGPRX2结合，通过荧光标记他克莫司在细胞中进行验证。长期服用他克莫司，初始过敏反应逐渐消失，MRGPRX2下调，导致炎症细胞因子释放减少(P)结论:短期服用他克莫司可通过MRGPRX2/B2诱导MCs假过敏反应，而长期服用他克莫司可下调MRGPRX2/B2的表达，这可能是其治疗多种皮肤病的有效免疫抑制作用的原因之一。

{"title":"Dual effect of tacrolimus on mast cell–mediated allergy and inflammation through Mas-related G protein-coupled receptor X2","authors":"Xueshan Du , Delu Che , Bin Peng , Yi Zheng , Yong Hao , Tao Jia , Xinyue Zhang , Songmei Geng","doi":"10.1016/j.jdermsci.2023.10.003","DOIUrl":"10.1016/j.jdermsci.2023.10.003","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Topical tacrolimus<span>, although widely used in the treatment of </span></span>dermatoses<span>, presents with an immediate irritation on initial application resembling a pseudo-allergic reaction. Mas-related G protein-coupled receptor X2 (MRGPRX2) in mast cells (MCs) mediates drug-induced pseudo-allergic reaction and immunoglobulin E (IgE)-independent pruritis in chronic skin diseases. However, the immunosuppression mechanism of tacrolimus on MCs </span></span><em>via</em> MRGPRX2 has not been reported.</p></div><div><h3>Objective</h3><p>To investigate the role of MRGPRX2 and the mechanism of action of tacrolimus on its short-term and long-term applications.</p></div><div><h3>Methods</h3><p>Wild-type mice, Kit<sup>W-sh/W-sh</sup> mice, and MrgprB2-deficient (MUT) mice were used to study the effect of tacrolimus on <em>in vivo</em> anaphylaxis model. LAD2 cells and MRGPRX2-knockdown LAD2 cells were specifically used to derive the associated mechanism of the tacrolimus effect.</p></div><div><h3>Results</h3><p>Short-term application of tacrolimus triggers IgE-independent activation of MCs <em>via</em> MRGPRX2/B2 in both <em>in vivo</em> and <em>in vitro</em><span> experiments. Tacrolimus binds to MRGPRX2, which was verified by fluorescently labeled tacrolimus in cells. On long-term treatment with tacrolimus, the initial allergic reaction fades away corresponding with the downregulation of MRGPRX2, which leads to decreased release of inflammatory cytokines (</span><em>P</em> < 0.05 to <em>P</em> < 0.001).</p></div><div><h3>Conclusion</h3><p>Short-term treatment with tacrolimus induces pseudo-allergic reaction <em>via</em><span> MRGPRX2/B2 in MCs, whereas long-term treatment downregulates expression of MRGPRX2/B2, which may contribute to its potent immunosuppressive effect in the treatment of various skin diseases.</span></p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89721335","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

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Journal of dermatological science

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀