Journal of dermatological science最新文献

{"title":"The cumulative effect of compound heterozygous variants in TRPV3 caused Olmsted syndrome.","authors":"Ran Mo, Xiaoqi Ma, Linghan Hu, Yingjian Tan, Lei Qiang, Yong Yang, Xiaoping Wang, Zhiming Chen","doi":"10.1016/j.jdermsci.2024.10.005","DOIUrl":"10.1016/j.jdermsci.2024.10.005","url":null,"abstract":"<p><strong>Background: </strong>Olmsted syndrome (OS) is a rare genodermatosis predominantly inherited in an autosomal dominant manner, typically arising from gain-of-function (GOF) variants in the transient receptor potential channel vanilloid 3 (TRPV3) gene.</p><p><strong>Objective: </strong>This study aims to investigate potential mechanisms underlying OS in two cases presenting with an autosomal recessive inheritance pattern.</p><p><strong>Methods: </strong>Next-generation sequencing panel was employed to identify TRPV3 variants. TRPV3 plasmids carrying specific point variations were generated and transiently transfected into HEK293T cells. Electrophysiological patch-clamp techniques were utilized to record voltage-activated and ligand-activated currents. Celltiter-Glo luminescent assay was employed to analyze the cell viabilities.</p><p><strong>Results: </strong>Compound heterozygous variants, c.1563 G>C (p.W521C) and c.1376 C>T (p.S459L), as well as c.1773 G>C (p.L591F) and c.2186 G>A (p.R729Q), were identified in the two OS patients respectively. Electrophysiological analysis of ligand-induced activation of TRPV3 variants demonstrated the closest correlation with clinical manifestations. All four variants displayed GOF channel activity characterized by increased sensitivity. Notably, W521C and L591F exhibited both heightened sensitivity and lower EC50 values for the TRPV3 agonist. Co-transfection with wild-type TRPV3 plasmids significantly rescued these effects. Cells co-transfected with the corresponding compound heterozygous variants exhibited intermediate electrophysiological characteristics.</p><p><strong>Conclusions: </strong>In this study, we present two cases of OS by autosomal-recessive inheritance of TPRV3 variants. This study presents a notable observation of compound heterozygous GOF variants in TRPV3, highlighting their cumulative impact on clinical manifestations. Additionally, we advocate for the use of ligand-dependent ion channel activity assays to assess the pathogenicity of TRPV3 variants in OS.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635163","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}

{"title":"The decrease in peripheral blood basophils in a mouse model of IgE-induced inflammation involves their migration to lymph nodes","authors":"Ni Ma ,&nbsp;Izumi Kishimoto ,&nbsp;Aki Tajima ,&nbsp;Noriko Kume ,&nbsp;Naotomo Kambe ,&nbsp;Hideaki Tanizaki","doi":"10.1016/j.jdermsci.2024.09.004","DOIUrl":"10.1016/j.jdermsci.2024.09.004","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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-<em>Kit</em>^<em>W</em><em>/Kit</em>^<em>W-v</em> mice were used to investigate the role of mast cells in this IgE-mediated model.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"116 2","pages":"Pages 61-69"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376422","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}

{"title":"Downregulation of carnitine acetyltransferase by promoter hypermethylation regulates ultraviolet-induced matrix metalloproteinase-1 expression in human dermal fibroblasts","authors":"Min Ji Song ,&nbsp;Min-Kyoung Kim ,&nbsp;Chi-Hyun Park ,&nbsp;Haesoo Kim ,&nbsp;Si Hyung Lee ,&nbsp;Dong Hun Lee ,&nbsp;Jin Ho Chung","doi":"10.1016/j.jdermsci.2024.09.005","DOIUrl":"10.1016/j.jdermsci.2024.09.005","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>We investigated changes in CRAT expression upon UV irradiation and its effect on MMP-1 expression.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>The expression of CRAT was decreased in UV-irradiated human skin <em>in vivo</em> and in human dermal fibroblasts <em>in vitro</em>. 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.</div></div><div><h3>Conclusion</h3><div>CRAT downregulation caused by promoter hypermethylation may play an important role in UV-induced skin aging via upregulation of MMP-1 expression.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"116 2","pages":"Pages 70-77"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515371","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}

{"title":"Genome-wide DNA methylation regulated by AHCY through SAM / SAH axis promotes psoriasis pathogenesis.","authors":"Lingxi Liu, Lihao Chen, Yu Hu, Qian Zhang, Kun Chen, Jiaan Zhang","doi":"10.1016/j.jdermsci.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2024.10.004","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic inflammatory skin disease that affects a significant proportion of the global population. The involvement of S-adenosine homocysteine hydrolase (AHCY) in psoriasis and its impact on DNA methylation have not been extensively studied.</p><p><strong>Objective: </strong>This study aimed to investigate the role of AHCY and its impact on DNA methylation in psoriasis pathogenesis.</p><p><strong>Methods: </strong>In the present study, we investigated the expression of AHCY in psoriatic lesions and assessed its association with the severity of the disease. Moreover, knockdown experiments were conducted to elucidate the impact of AHCY on psoriatic symptoms, keratinocyte proliferation, and aberrant differentiation. Furthermore, alterations in DNA methylation patterns resulting from AHCY knockdown were analyzed.</p><p><strong>Results: </strong>Our findings revealed that AHCY was upregulated in psoriatic lesions and exhibited a positive correlation with disease severity. Knockdown of AHCY alleviated psoriatic symptoms, inhibited keratinocyte proliferation, and prevented abnormal differentiation. Moreover, AHCY knockdown led to reduced levels of DNA methylation and alterations in methylation patterns. Notably, differential methylation was observed at specific gene loci associated with psoriasis-related inflammation.</p><p><strong>Conclusion: </strong>This study highlights the potential role of AHCY in psoriasis development through its influence on DNA methylation. The findings underscore the complex interaction among AHCY, epigenetic modifications, and inflammation in the pathogenesis of psoriasis. Consequently, AHCY may serve as a promising therapeutic target for psoriasis treatment.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635161","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}

{"title":"A carbamazepine metabolite activates NLRP3 and controls skin homing of CD8⁺ T-cells in SJS/TEN.","authors":"Chen Zhang, Pei Qiao, JieYu Zhang, YiXin Luo, ChunYing Xiao, ShengXian Shen, Akio Hasegawa, HongJiang Qiao, Gang Wang, Riichiro Abe, Meng Fu","doi":"10.1016/j.jdermsci.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2024.10.003","url":null,"abstract":"<p><strong>Background: </strong>Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse drug reactions with extensive keratinocyte death. Carbamazepine (CBZ), the most commonly implicated drug in SJS/TEN, is metabolized by the cytochrome P450 enzyme 3A4 (CYP3A4) into carbamazepine-10,11-epoxide (CBZE) in the liver. While CD8⁺ cytotoxic T cells play an important role in SJS/TEN, the underlying mechanism of exuberant immune response by CD8⁺ T cells in these conditions remains incompletely understood.</p><p><strong>Objectives: </strong>To examine the expression of NLRP3 inflammasome and their skin migration in CBZE-induced SJS/TEN.</p><p><strong>Methods: </strong>The expression of the NLRP3 inflammasome complex in skin lesions, sera, and blister fluids of SJS/TEN patients were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay. NLRP3 formation and CD8⁺ T cell activation status and their functions were examined by immunoblotting, immunofluorescence, and chemotaxis assays.</p><p><strong>Results: </strong>The expression of the NLRP3 inflammasome complex was greatly increased in skin lesions of SJS/TEN patients. Moreover, IL-1β and IL-18 levels in sera and blister fluids of SJS/TEN patients were approximately 3-fold higher than those in healthy individuals, with a linear correlation between IL-1β levels and disease activity. CBZE induced NLRP3 inflammasome formation, upregulated CXCL9/CXCL10 levels, and activated CD8⁺ cytotoxic T cell functions via IL-1β/IL-1R or IL-18/IL-18R signaling in SJS/TEN keratinocytes, which promoted CD8⁺ cytotoxic T cell migration in SJS/TEN patients.</p><p><strong>Conclusion: </strong>This study showed that CBZE promoted NLRP3 inflammasome formation and strengthened the activation and function of CD8⁺ cytotoxic T cells in the skin, which contributed to the initiation and progression of SJS/TEN.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585434","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}

{"title":"P2X7R-primed keratinocytes are susceptible to apoptosis via GPCR-Gβγ-pERK signal pathways.","authors":"Tomoki Nishiguchi, Haruna Kimura, Yuki Saito, Takeaki Ozawa, Riichiro Abe, Akito Hasegawa","doi":"10.1016/j.jdermsci.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2024.10.001","url":null,"abstract":"<p><strong>Background: </strong>Cell death constitutes a pivotal biological phenomenon essential for the preservation of homeostasis within living organisms. In the context of maintaining a functional skin barrier, keratinocytes exert positively and negatively control cell death signals. However, in patients with severe drug eruptions, anomalous overexpression of the formyl peptide receptor 1 (FPR1) in keratinocytes elicits a distinctive mode of cell death known as necroptosis, thereby suffering a loss of the skin barrier. The precise molecular mechanisms connecting FPR1 activation to this cell death remain unclear.</p><p><strong>Objective: </strong>We have investigated the intracellular signal transduction cascade governing FPR1-mediated cell death in cultured keratinocytes.</p><p><strong>Methods: </strong>We used HaCaT cells as a model keratinocyte. The expression of FPR1 was detected with qPCR. The presence of cell death events was monitored through live-cell fluorescent staining and LDH release assays. Furthermore, the phosphorylation of ERK was assessed via Western blot analysis. Intracellular signal pathways were investigated using specific inhibitors.</p><p><strong>Results: </strong>Ligand stimulation of an endogenous ion channel, purinergic receptor P2X7 (P2X7R), increased the FPR1 expression level. This upregulated FPR1 demonstrated functional competence in the phosphorylation of downstream MAP kinase and the initiation of cell death. Notably, this cell death was ameliorated upon the administration of inhibitors targeting Gβγ, ERK, and caspases.</p><p><strong>Conclusion: </strong>The induction and stimulation of FPR1 initiated apoptosis in keratinocytes via the Gβγ-pERK signaling pathway. Our findings postulate that the downstream components of FPR1 represent an alternative therapeutic target for preventing unintended keratinocyte cell death.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515372","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}

{"title":"Staphylococcus epidermidis augments human β-defensin-3 synthesis through the transforming growth factor alpha-epidermal growth factor receptor cascade","authors":"Rie Ommori,&nbsp;Satoru Shinkuma,&nbsp;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}

{"title":"Dermal fibroblasts retain site-specific transcriptomic identity in keloids","authors":"Pingping Lin ,&nbsp;Daoning Zhang ,&nbsp;Jie Tian ,&nbsp;Binbin Lai ,&nbsp;Yu Yang ,&nbsp;Yicen Yan ,&nbsp;Shenxi Zhang ,&nbsp;Guohong Zhang ,&nbsp;Hang Li","doi":"10.1016/j.jdermsci.2024.08.002","DOIUrl":"10.1016/j.jdermsci.2024.08.002","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>This study aimed to assess whether the spatial heterogeneity and positional identity observed in different anatomic sites persist in keloids.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"116 1","pages":"Pages 41-49"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335259","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}

{"title":"Dysbiosis-activated IL-17-producing T cells promote skin immunopathological progression in mice deficient of the Notch ligand Jag1 in keratinocytes","authors":"Eun Hyeon Song ,&nbsp;Juan Garcia Jr. ,&nbsp;Na Xiong","doi":"10.1016/j.jdermsci.2024.09.001","DOIUrl":"10.1016/j.jdermsci.2024.09.001","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>To dissect molecular and cellular mechanisms underlying development of skin immunopathology in mice defective of the Notch ligand Jagged-1 (Jag1).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"116 1","pages":"Pages 14-23"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304942","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}

{"title":"Possible facilitating role of IL-17A on IL-23 production in keratinocytes in psoriatic lesions","authors":"Akimasa Adachi ,&nbsp;Tetsuya Honda ,&nbsp;Nobuhiro Kusuba ,&nbsp;Fuuka Minami ,&nbsp;Satoshi Nakamizo ,&nbsp;Kenji Kabashima","doi":"10.1016/j.jdermsci.2024.09.002","DOIUrl":"10.1016/j.jdermsci.2024.09.002","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"116 1","pages":"Pages 50-54"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335260","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}