JID innovations : skin science from molecules to population health最新文献

{"title":"Uncommon Variants in FLG2 and NOD2 Are Associated with Atopic Dermatitis in the Ethiopian Population","authors":"Sailan Wang ,&nbsp;Julia K. Elmgren ,&nbsp;Jesper Eisfeldt ,&nbsp;Samina Asad ,&nbsp;Marlene Ek ,&nbsp;Kassahun Bilcha ,&nbsp;Annisa Befekadu ,&nbsp;Carl-Fredrik Wahlgren ,&nbsp;Magnus Nordenskjöld ,&nbsp;Fulya Taylan ,&nbsp;Isabel Tapia-Paez ,&nbsp;Maria Bradley","doi":"10.1016/j.xjidi.2024.100284","DOIUrl":"https://doi.org/10.1016/j.xjidi.2024.100284","url":null,"abstract":"<div><p>Loss-of-function variants in the <em>FLG</em> gene have been identified as the strongest cause of susceptibility to atopic dermatitis (AD) in Europeans and Asians. However, very little is known about the genetic etiology behind AD in African populations, where the prevalence of AD is notably high. We sought to investigate the genetic origins of AD by performing whole-genome sequencing in an Ethiopian family with 12 individuals and several affected in different generations. We identified 2 variants within <em>FLG2</em> (p.D13Y) and <em>NOD2</em> (p.A918S) genes cosegregating with AD in the affected individuals. Further genotyping analyses in both Ethiopian and Swedish AD cases and controls revealed a significant association with the <em>FLG2</em> variant (p.D13Y, <em>P</em> &lt; .0013) only in the Ethiopian cohort. However, the <em>NOD2</em> variant (p.A918S) did not show any association in our Ethiopian cohort. Instead, 2 previously recognized <em>NOD2</em> variants (p.A849V, <em>P</em> &lt; .0085 and p.G908R, <em>P</em> &lt; .0036) were significantly associated with AD in our Ethiopian cohort. Our study indicates that the <em>FLG2</em> and <em>NOD2</em> genes might be important in the etiology of AD in Ethiopians. Additional genetic and functional studies are needed to confirm the role of these genes and the associated variants into the development of AD.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100284"},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000316/pdfft?md5=bec2a0d2f591ecbc0d7676ce6610e673&pid=1-s2.0-S2667026724000316-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141078095","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}

{"title":"The WD Domain of Atg16l1 Crucial for LC3-Associated Phagocytosis Is Not Required for Preserving Skin Barrier Function in Mice","authors":"Shannon Conway ,&nbsp;Matthew Jefferson ,&nbsp;Derek T. Warren ,&nbsp;Thomas Wileman ,&nbsp;Christopher J. Morris","doi":"10.1016/j.xjidi.2024.100283","DOIUrl":"https://doi.org/10.1016/j.xjidi.2024.100283","url":null,"abstract":"<div><p>The skin is a multifunctional organ, forming a barrier between the external and internal environment, thereby functioning as a safeguard against extrinsic factors. Autophagy has been implicated in epidermal differentiation and in preserving skin homeostasis. LC3-associated phagocytosis (LAP) uses some but not all components of autophagy. The <em>Atg16l1</em> (<span><math><mrow><mo>Δ</mo></mrow></math></span> WD) mouse model lacks the WD40 domain required for LAP and has been widely used to study the effects of LAP deficiency and autophagy on tissue homeostasis and response to infection.</p><p>In this study, the <span><math><mrow><mo>Δ</mo></mrow></math></span> WD model was used to study the relationship between LAP and skin homeostasis by determining whether LAP-deficient mice display a cutaneous phenotype. Skin histology of wild-type and <span><math><mrow><mo>Δ</mo></mrow></math></span> WD mice aged 1 year revealed minor morphological differences in the tail skin dermal layer. RT-qPCR and western blot analysis showed no differences in key keratin expression between genotypes. Skin barrier formation, assessed by dye permeation assays, demonstrated full and proper formation of the skin barrier at embryonic day 18.5 in both genotypes. Biomechanical analysis of the skin showed decreased skin elasticity in aged <span><math><mrow><mo>Δ</mo></mrow></math></span> WD but not wild-type mice. In summary, the LAP-deficient <span><math><mrow><mo>Δ</mo></mrow></math></span> WD mice displayed subtle alterations in dermal histology and age-related biomechanical changes.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100283"},"PeriodicalIF":0.0,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000304/pdfft?md5=73a0a543379462b38dc018cd64d19be3&pid=1-s2.0-S2667026724000304-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141083217","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}

{"title":"Diacron-Reactive Oxygen Metabolites Levels Are Initially Elevated in Patients with Bullous Pemphigoid","authors":"Nagie Tozaki ,&nbsp;Chisato Tawada ,&nbsp;Kayoko Tanaka ,&nbsp;Dongjun Im ,&nbsp;Keisuke Ueda ,&nbsp;Noriko Kato ,&nbsp;Hiromu Tsuji ,&nbsp;Yuka Yoshie ,&nbsp;Maho Matsuo ,&nbsp;Naohisa Ichiki ,&nbsp;Hirofumi Niwa ,&nbsp;Yoko Mizutani ,&nbsp;En Shu ,&nbsp;Hiroaki Iwata","doi":"10.1016/j.xjidi.2024.100282","DOIUrl":"10.1016/j.xjidi.2024.100282","url":null,"abstract":"<div><p>ROS are involved in the pathogenesis of bullous pemphigoid (BP), but this involvement has not been fully elucidated. In this study, to further elucidate the pathogenic role of ROS in BP, we examined the results of the diacron-reactive oxygen metabolite test and the biological antioxidant potential test for 16 patients with BP who visited our hospital before being treated with systemic corticosteroids. In the patients with BP, the average diacron-reactive oxygen metabolite levels, expressed in Carratelli units, were significantly reduced at 1 month of treatment (from 335.6 ± 40.3 Carratelli units to 224.7 ± 61.6 Carratelli units, <em>P</em> &lt; .001). Bullous Pemphigoid Disease Area Index (erosions/blisters) scores correlated with diacron-reactive oxygen metabolite levels (<em>r</em> = 0.51), suggesting that those levels reflect the disease severity. We also performed staining of 3,5-dibromotyrosine in skin tissues. The 3,5-dibromotyrosine is expected to be a marker of tissue damage related to inflammation and allergies. The 3,5-dibromotyrosine was stained in infiltrated cells around the dermis, throughout the blister fluid, and at the basement membrane within the blister. It is considered that tissue destruction caused by the myeloperoxidase released from neutrophils and by eosinophil peroxidase released from eosinophils is involved in blister formation. The results suggest that ROS play a role in BP.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100282"},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000298/pdfft?md5=1aa4f76ea822f8c8271d1c987c7f0492&pid=1-s2.0-S2667026724000298-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140761948","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}

{"title":"Dupilumab Therapy Modulates Circulating Inflammatory Mediators in Patients with Prurigo Nodularis","authors":"Aaron Bao ,&nbsp;Emily Ma ,&nbsp;Hannah Cornman ,&nbsp;Anusha Kambala ,&nbsp;Jaya Manjunath ,&nbsp;Alexander L. Kollhoff ,&nbsp;Brenda Umenita Imo ,&nbsp;Madan M. Kwatra ,&nbsp;Shawn G. Kwatra","doi":"10.1016/j.xjidi.2024.100281","DOIUrl":"10.1016/j.xjidi.2024.100281","url":null,"abstract":"<div><p>Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus and skin nodules. Beyond the skin, PN involves circulating blood inflammation that may contribute to systemic disease comorbidities. Dupilumab was recently approved for treatment of PN, but its effects on systemic inflammation are unknown. Thus, we aimed to characterize changes in plasma concentrations of inflammatory proteins after dupilumab treatment. In this exploratory study, plasma samples were collected from 3 patients with moderate-to-severe PN before and after ≥6 months of dupilumab treatment. All patients exhibited clinically significant improvements after treatment. Of the 2569 proteins tested, 186 were differentially expressed after treatment (q &lt; 0.1, fold change &gt; 1.3). Downregulated proteins included cytokines associated with T helper (Th) 1 (IFN-γ, TNF-α), Th2 (IL-4, IL-13), and Th17/Th22 (IL-6, IL-22) signaling. Markers of innate immunity (IL-19, toll-like receptor 1, nitric oxide synthase 2), immune cell migration (CCL20, CD177), and fibrosis (IL-11, IL-22) were also decreased (q &lt; 0.1). Gene set variation analysis of Th2, Th17, and epithelial–mesenchymal transition gene sets showed reduced pathway expression in the post-treatment cohort (<em>P</em> &lt; .05). Plasma cytokine levels of IL-11, nitric oxide synthase 2, IL-13, IL-4, and IFNG (R² &gt; 0.75, q &lt; 0.10) showed the strongest correlations with pruritus severity. Dupilumab may reduce systemic inflammatory proteins associated with multiple immune and fibrosis pathways in patients with PN, potentially modulating the development of systemic disease comorbidities.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100281"},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000286/pdfft?md5=cdd3b5890486459ab549c6d845f2d8b1&pid=1-s2.0-S2667026724000286-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140780728","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}

{"title":"Atopic Dermatitis Complicated by Recurrent Eczema Herpeticum Is Characterized by Multiple, Concurrent Epidermal Inflammatory Endotypes","authors":"Nathan D. Jackson ,&nbsp;Nathan Dyjack ,&nbsp;Elena Goleva ,&nbsp;Lianghua Bin ,&nbsp;Michael T. Montgomery ,&nbsp;Cydney Rios ,&nbsp;Jamie L. Everman ,&nbsp;Patricia Taylor ,&nbsp;Caroline Bronchick ,&nbsp;Brittany N. Richers ,&nbsp;Donald Y.M. Leung ,&nbsp;Max A. Seibold","doi":"10.1016/j.xjidi.2024.100279","DOIUrl":"https://doi.org/10.1016/j.xjidi.2024.100279","url":null,"abstract":"<div><p>A subgroup of patients with atopic dermatitis (AD) suffers from recurrent, disseminated herpes simplex virus skin infection, termed eczema herpeticum. To determine the transcriptional mechanisms of the skin and immune system pathobiology that underlie development of AD with eczema herpeticum (ADEH), we performed RNA-sequencing analysis of nonlesional skin (epidermis, dermis) from AD patients with and without a history of ADEH (ADEH⁺, n = 15; ADEH⁻, n = 13) along with healthy controls (n = 15). We also performed RNA sequencing on participants’ plasmacytoid dendritic cells infected in vitro with herpes simplex virus 1. ADEH⁺ patients exhibited dysregulated gene expression, limited in the dermis (14 differentially expressed genes) and more widespread in the epidermis (129 differentially expressed genes). ADEH⁺-upregulated epidermal differentially expressed genes were enriched in type 2 cytokine (<em>IL4R</em><em>, CCL22</em>, <em>CRLF2</em>, <em>IL7R</em>), interferon (<em>CXCL10, ICAM1, IFI44</em>, <em>IRF7)</em>, and IL-36γ (<em>IL36G</em>) inflammatory gene pathways. All ADEH⁺ participants exhibited type 2 cytokine and inteferon endotypes, and 87% were IL36G-high. In contrast, these endotypes were more variably expressed among ADEH⁻ participants. ADEH⁺ skin also had dysregulated epidermal differentiation complex gene expression of the late-cornified envelope, S100A, and small proline-rich gene families, which are involved in skin barrier function and antimicrobial activities. Plasmacytoid dendritic cell transcriptional responses to herpes simplex virus 1 infection were unaltered by ADEH status. The study concluded that the pathobiology underlying ADEH⁺ risk is associated with a unique, multifaceted epidermal inflammation that accompanies dysregulation of epidermal differentiation complex genes. These findings will help direct future studies that define how these inflammatory patterns may drive risk of eczema herpeticum in AD.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100279"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000262/pdfft?md5=7b6c1e4f91cfb55dc901152bd521aa30&pid=1-s2.0-S2667026724000262-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428753","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}

{"title":"Whole-Transcriptome Sequencing–Based Profiling of the Cutaneous Virome in Patients with Secondary Immunodeficiency","authors":"Leila Youssefian ,&nbsp;Amir Hossein Saeidian ,&nbsp;Zahra Saffarian ,&nbsp;Mona Ariamanesh ,&nbsp;Fahimeh Abdollahimajd ,&nbsp;Sara Molkara ,&nbsp;Mohammad Shahidi-Dadras ,&nbsp;Reem Diab ,&nbsp;Fatemeh Vahidnezhad ,&nbsp;Sirous Zeinali ,&nbsp;Vivien Béziat ,&nbsp;Emmanuelle Jouanguy ,&nbsp;Jean-Laurent Casanova ,&nbsp;Jouni Uitto ,&nbsp;Hassan Vahidnezhad","doi":"10.1016/j.xjidi.2024.100278","DOIUrl":"10.1016/j.xjidi.2024.100278","url":null,"abstract":"<div><p>Most viral infections can be self-limited, with no requirement for medical intervention. However, the same viruses can cause severe diseases in patients with compromised immunity due to single-gene diseases, acquired immune deficiency syndrome, or hematologic malignancies or those receiving immunosuppressive drugs. Occasionally, these immunocompromised patients harbor &gt;1 infectious agent, requiring several concomitant diagnostic tests. We have developed, to our knowledge, a previously unreported whole-transcriptome sequencing–based pipeline that allows virome profiling, quantitation, and expression pattern analysis of 926 distinct viruses by sequencing of RNA isolated from a single lesional skin biopsy. This pipeline can also explore host genetics if there is a Mendelian predisposition to infection. We applied this pipeline to 6 Iranian patients with viral-induced skin lesions associated with immune deficiency secondary to HIV, human T-lymphotropic virus 1, chronic lymphocytic leukemia, and post transplant immunosuppression. In 5 cases, definitive human papillomavirus infections were identified, some caused by multiple viral types. In addition to human papillomavirus, coinfection with other viruses (Merkle cell polyomavirus, cytomegalovirus, and human herpesvirus 4) was detected in some lesions. In 1 case, whole-transcriptome sequencing validated the clinical diagnosis of adult T-cell leukemia/lymphoma in a patient with an initial diagnosis of mycosis fungoides/Sézary syndrome. These findings attest to the power of whole-transcriptome sequencing in profiling the cutaneous virome in the context of compromised immunity.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100278"},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000250/pdfft?md5=88c25bdb591819f9dafffaa0fab0b9cf&pid=1-s2.0-S2667026724000250-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140404884","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}

{"title":"Testing the Reliability of Optical Coherence Tomography to Measure Epidermal Thickness and Distinguish Volar and Nonvolar Skin","authors":"Molly E. Baumann ,&nbsp;Nina Rossa Haddad ,&nbsp;Alyssa Salazar ,&nbsp;W. Lee Childers ,&nbsp;Shawn Farrokhi ,&nbsp;Neil B. Goldstein ,&nbsp;Brad D. Hendershot ,&nbsp;Lisa Reider ,&nbsp;Richard E. Thompson ,&nbsp;Michael S. Valerio ,&nbsp;Christopher L. Dearth ,&nbsp;Luis A. Garza ,&nbsp;Major Extremity Trauma Research Consortium (METRC)","doi":"10.1016/j.xjidi.2024.100276","DOIUrl":"10.1016/j.xjidi.2024.100276","url":null,"abstract":"<div><p>In persons with limb loss, prosthetic devices cause skin breakdown, largely because residual limb skin (nonvolar) is not intended to bear weight such as palmoplantar (volar) skin. Before evaluation of treatment efficacy to improve skin resiliency, efforts are needed to establish normative data and assess outcome metric reliability. The purpose of this study was to use optical coherence tomography to (i) characterize volar and nonvolar skin epidermal thickness and (ii) examine the reliability of optical coherence tomography. Four orientations of optical coherence tomography images were collected on 33 volunteers (6 with limb loss) at 2 time points, and the epidermis was traced to quantify thickness by 3 evaluators. Epidermal thickness was greater (<em>P</em> &lt; .01) for volar skin (palm) (265.1 ± 50.9 μm, n = 33) than for both nonvolar locations: posterior thigh (89.8 ± 18.1 μm, n = 27) or residual limb (93.4 ± 27.4 μm, n = 6). The inter-rater intraclass correlation coefficient was high for volar skin (0.887–0.956) but low for nonvolar skin (thigh: 0.292–0.391, residual limb: 0.211–0.580). Correlation improved when comparing only 2 evaluators who used the same display technique (palm: 0.827–0.940, thigh: 0.633–0.877, residual limb: 0.213–0.952). Despite poor inter-rater agreement for nonvolar skin, perhaps due to challenges in identifying the dermal–epidermal junction, this study helps to support the utility of optical coherence tomography to distinguish volar from nonvolar skin.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100276"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000237/pdfft?md5=ca164c01d75d7275d0fa882b22a3633a&pid=1-s2.0-S2667026724000237-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140272024","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}

{"title":"Proceedings of the Gunnar Lomholt Symposium during the IPC 2023 Think Tank at Faroe Islands, Friday, September 8, 2023","authors":"Francis Yi Xing Lai ,&nbsp;Hervé Bachelez ,&nbsp;Johann Gudjonsson ,&nbsp;Lone Skov ,&nbsp;Claus Zachariae ,&nbsp;Peter C.M. van de Kerkhof ,&nbsp;Jonathan N.W.N. Barker","doi":"10.1016/j.xjidi.2024.100267","DOIUrl":"10.1016/j.xjidi.2024.100267","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100267"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000134/pdfft?md5=64fd1f496d1d8561591613579f2475a0&pid=1-s2.0-S2667026724000134-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139883479","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}

{"title":"Downregulation of Caveolae-Associated Proteins in Psoriasis: A Case Series Study","authors":"Deborah A. Lin ,&nbsp;Beatriz Abdo Abujamra ,&nbsp;Stephanie Revah ,&nbsp;Leigh Nattkemper ,&nbsp;Brian Morrison ,&nbsp;Paolo Romanelli ,&nbsp;Ivan Jozic","doi":"10.1016/j.xjidi.2024.100265","DOIUrl":"10.1016/j.xjidi.2024.100265","url":null,"abstract":"<div><p>We have previously identified that a structural membrane protein Caveolin-1 (Cav1) is involved in the regulation of aberrant keratinocyte proliferation and differentiation. The aim of this study was to elucidate the role of Cav1, Caveolin-2 (Cav2), and Cavin-1 in the pathogenesis of psoriasis vulgaris and between psoriasis subtypes. We utilized human biopsies from validated cases of psoriasis vulgaris (n = 21) at the University of Miami Hospital and compared the expression of Cav1, Cav2, and Cavin-1 by immunohistochemistry staining with that in normal healthy age-/sex-/location-matched skin (n = 15) and chronic spongiotic dermatitis skin samples (as control inflammatory skin condition) and quantified using QuPath. Distinct subtypes of psoriasis included guttate, inverse, nail, plaque, palmoplantar, and pustular. All biopsy samples exhibited a trend toward downregulation of Cav1, with nail, plaque, and palmoplantar psoriasis exhibiting the most pronounced effects. Only nail and pustular psoriasis samples exhibited significant downregulation of Cav2 and Cavin-1, suggesting Cav1 to be the main caveolar contributor to the pathogenesis of psoriasis. Together, these data support caveolae as pathophysiological targets in nail and pustular psoriasis, whereas Cav1 seems to be a general biomarker of multiple subtypes of psoriasis.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100265"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000110/pdfft?md5=9f2e78ab69fefc00700771ebaf34c34b&pid=1-s2.0-S2667026724000110-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139879302","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}

{"title":"Assessing Longitudinal Treatment Efficacies and Alterations in Molecular Markers Associated with Glutamatergic Signaling and Immune Checkpoint Inhibitors in a Spontaneous Melanoma Mouse Model","authors":"Kevinn Eddy ,&nbsp;Kajal Gupta ,&nbsp;Mohamad Naser Eddin ,&nbsp;Christina Marinaro ,&nbsp;Sanjana Putta ,&nbsp;John Michael Sauer Jr ,&nbsp;Anna Chaly ,&nbsp;Katie B. Freeman ,&nbsp;Jeffrey C. Pelletier ,&nbsp;Anna Fateeva ,&nbsp;Philip Furmanski ,&nbsp;Ann W. Silk ,&nbsp;Allen B. Reitz ,&nbsp;Andrew Zloza ,&nbsp;Suzie Chen","doi":"10.1016/j.xjidi.2024.100262","DOIUrl":"10.1016/j.xjidi.2024.100262","url":null,"abstract":"<div><p>Previous work done by our laboratory described the use of an immunocompetent spontaneous melanoma-prone mouse model, TGS (TG-3/SKH-1), to evaluate treatment outcomes using inhibitors of glutamatergic signaling and immune checkpoint for 18 weeks. We showed a significant therapeutic efficacy with a notable sex-biased response in male mice. In this follow-up 18-week study, the dose of the glutamatergic signaling inhibitor was increased (from 1.7 mg/kg to 25 mg/kg), which resulted in improved responses in female mice but not male mice. The greatest reduction in tumor progression was observed in male mice treated with single-agent troriluzole and anti–PD-1. Furthermore, a randomly selected group of mice was removed from treatment after 18 weeks and maintained for up to an additional 48 weeks demonstrating the utility of the TGS mouse model to perform a ≥1-year preclinical therapeutic study in a physiologically relevant tumor–host environment. Digital spatial imaging analyses were performed in tumors and tumor microenvironments across treatment modalities using antibody panels for immune cell types and immune cell activation. The results suggest that immune cell populations and cytotoxic activities of T cells play critical roles in treatment responses in these mice. Examination of a group of molecular protein markers based on the proposed mechanisms of action of inhibitors of glutamatergic signaling and immune checkpoint showed that alterations in expression levels of xCT, γ-H2AX, EAAT2, PD-L1, and PD-1 are likely associated with the loss of treatment responses. These results suggest the importance of tracking changes in molecular markers associated with the mechanism of action of therapeutics over the course of a longitudinal preclinical therapeutic study in spatial and temporal manners.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100262"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000080/pdfft?md5=31a2703b3576a894a7599aeea3188176&pid=1-s2.0-S2667026724000080-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139539600","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}