{"title":"A Newly Identified Spliceosomal Protein AHED is Essential for Homeostasis of the Epidermis.","authors":"Mikiro Takaishi, Tatsushi Ishimoto, Sayo Kataoka, Ken-Ichi Yagyu, Keiko Morisawa, Sonoko Kinjo, Kazuho Ikeo, Shohei Noma, Chitose Takahashi, Yasushi Okazaki, Masahiro Tokunaga, Chikara Kokubu, Junji Takeda, Shigetoshi Sano","doi":"10.1016/j.jid.2025.01.025","DOIUrl":"https://doi.org/10.1016/j.jid.2025.01.025","url":null,"abstract":"<p><p>To identify genes that are essential for the functions of cells and organs, we established a homozygous mutant mouse embryonic stem cell bank from which we identified a gene, named Attenuated Hematopoietic Development (Ahed), that plays an essential role in hematopoiesis. Here, we characterize the role of AHED in the skin by analyzing mice with an epidermis-specific Ahed deficiency. Those mice have apoptotic cells in their epidermis from the perinatal stage. Thereafter, they develop skin barrier disruptions over time, which cause lethality soon after birth. Experiments using inducible Ahed deletion in vivo and in vitro revealed that an Ahed deficiency leads to keratinocyte apoptosis, impairs keratinocyte proliferation, and promotes dermatitis development. Since we found that AHED is a nuclear protein, we further revealed that AHED interacts with known spliceosomal proteins in HeLa cells. Moreover, altered splicing mRNA patterns were demonstrated in Ahed deficient keratinocytes. These results suggest that AHED plays a crucial role in the maintenance of epidermal integrity, and more importantly, it contributes to mRNA splicing that is essential for multiple cell lineages.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470408","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 Differential Roles of HSP90 Isoforms in Skin Inflammation: Anti-Inflammatory Potential of TRAP1 Inhibition.","authors":"Hakim Ben Abdallah, Lars Iversen, Claus Johansen","doi":"10.1016/j.jid.2025.02.006","DOIUrl":"10.1016/j.jid.2025.02.006","url":null,"abstract":"<p><p>HSP90, a molecular chaperone, has been identified as a drug target in inflammatory skin diseases. However, 4 different HSP90 isoforms (HSP90α, HSP90β, GRP94, and TRAP1) exist. Therefore, this study aimed to evaluate the functional role of the HSP90 isoforms in skin inflammation. Selective knockdown of the HSP90 isoforms revealed different inflammatory effects in stimulated keratinocytes. TRAP1 knockdown significantly downregulated the expression of the measured inflammatory genes (IL1B, IL6, IL17C, IL23A, IL19, IL36G, CXCL8, CCL5, CCL17, CCL20). Selective and combined knockdown of HSP90α and HSP90β showed a trend toward increased inflammatory activity. Selective GRP94 knockdown and combined knockdown of the organelle-specific isoforms (GRP94 + TRAP1) or all 4 isoforms resulted in inconsistent effects. In addition, a selective TRAP1 inhibitor (gamitrinib) suppressed the inflammatory gene expression in keratinocytes and fibroblasts (IL17C, IL23A, IL36G) and in hidradenitis suppurativa skin cultured ex vivo (IL1B, IL6, CXCL8, IL17A, IL36G). In conclusion, selective and simultaneous knockdown of the HSP90 isoforms mediated different inflammatory effects, revealing that the HSP90 isoforms have distinct roles in skin inflammation. In addition, we discovered that inhibition of TRAP1 exerted consistent anti-inflammatory effects, suggesting that TRAP1 inhibitors may represent a topical therapeutic strategy for inflammatory skin diseases.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470410","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}
Florentine de Boer, Sanja Kezic, Ghislaine van der Lelie, Ehsan Motazedi, Thomas Rustemeyer, Arjan van Dijk, Mitra Almasian, Ivone Jakasa, Henk F van der Molen
{"title":"Effect of Repeated Low-Dose UVR Exposure on Skin Inflammation Threshold, Skin Biomarkers, and Vitamin D in Healthy Adults.","authors":"Florentine de Boer, Sanja Kezic, Ghislaine van der Lelie, Ehsan Motazedi, Thomas Rustemeyer, Arjan van Dijk, Mitra Almasian, Ivone Jakasa, Henk F van der Molen","doi":"10.1016/j.jid.2025.01.024","DOIUrl":"10.1016/j.jid.2025.01.024","url":null,"abstract":"<p><p>UVR can cause photoaging, skin burns, and skin cancer. The skin counters these effects through photoadaptation, which involves melanin production, skin thickening, and immune responses. This study investigated the effects of repeated, suberythemal low-dose UVR on the skin's inflammation threshold, assessed as minimal erythema dose, across different skin phototypes. In addition, epidermal and stratum corneum thickness, melanin index, erythema index, skin and blood levels of immunological biomarkers, and blood vitamin D3 25(OH) were measured. Over 9 weeks, 31 subjects were exposed to UVR (0.8 standard erythema dose) on the lower back 3 times per week. Results showed a 50% increase in minimal erythema dose, with a stronger effect in lighter phototypes. Increase in minimal erythema dose was paralleled by an increase in erythema index. Melanin index and stratum corneum thickness increased significantly by 12 and 34%, respectively, with melanin having a stronger effect on the minimal erythema dose increase. Vitamin D levels rose by 21%, adjusting for seasonal decline. Immunological markers of T helper 1/T helper 2 response and vascular markers declined, indicating local immunosuppression, although no systemic changes in immunological markers were observed. These findings suggest that even low UVR doses are sufficient to induce photoadaptation. Further research is needed to evaluate the long-term benefits and risks of this exposure.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434857","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}
Ali Azimi, Lei Bi, Anila Bonfil, Rachel Teh, Helena Collgros, Jinman Kim, Pablo Fernandez-Penas
{"title":"Integrated Analysis of Proteomic and Dermoscopy Imaging Data Improves Noninvasive Classification of Benign Nevi and Melanoma.","authors":"Ali Azimi, Lei Bi, Anila Bonfil, Rachel Teh, Helena Collgros, Jinman Kim, Pablo Fernandez-Penas","doi":"10.1016/j.jid.2025.01.022","DOIUrl":"10.1016/j.jid.2025.01.022","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426760","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}
Nathan C Balukoff, Garrett Houk, Tammy Gonzalez, Yael Berton, Vincent Ronfard, Irena Pastar, Marjana Tomic-Canic
{"title":"Out of this World: Wound Healing on Earth and in Space.","authors":"Nathan C Balukoff, Garrett Houk, Tammy Gonzalez, Yael Berton, Vincent Ronfard, Irena Pastar, Marjana Tomic-Canic","doi":"10.1016/j.jid.2024.12.024","DOIUrl":"https://doi.org/10.1016/j.jid.2024.12.024","url":null,"abstract":"<p><p>Impaired wound healing is a significant concern for humans in space, where the unique microgravity environment poses challenges to the natural healing processes of the body. Similar to chronic wounds on earth, such as diabetic foot ulcers and venous leg ulcers, wounds inflicted in space exhibit delayed or impaired healing responses. These wounds share common features, including dysregulated cellular signaling, altered cytokine profiles, and impaired tissue regeneration. Little is known about the mechanisms underlying wound healing under microgravity. In this review, we focused on exploring the parallels between wound healing in space and chronic wounds on earth as a fundamental approach for developing effective countermeasures to promote healing and mitigate associated health risks during long-space missions.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426761","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}
Jiaqi Feng, Mingmin Xu, Jue Qi, Wenjuan Wu, Minsheng Peng, Li He
{"title":"Whole-Genome Structural Variations Study in a Severe Acne Family.","authors":"Jiaqi Feng, Mingmin Xu, Jue Qi, Wenjuan Wu, Minsheng Peng, Li He","doi":"10.1016/j.jid.2025.01.023","DOIUrl":"10.1016/j.jid.2025.01.023","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426764","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 Role of IL-23 Inhibition in Reduction of Circulating IL-17A<sup>+</sup> CD103<sup>+</sup> Memory CD8 T Cells in Psoriasis.","authors":"Yutaka Matsumura, Miki Kume, Junichi Furuta, Hanako Koguchi-Yoshioka, Manabu Fujimoto, Rei Watanabe","doi":"10.1016/j.jid.2025.01.021","DOIUrl":"10.1016/j.jid.2025.01.021","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416635","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}
Eva Rawlings Parker, Misha Rosenbach, Mark Denis P Davis
{"title":"The Voice of the American Dermatological Association: 2025 Official Policy Statement on Climate Change.","authors":"Eva Rawlings Parker, Misha Rosenbach, Mark Denis P Davis","doi":"10.1016/j.jid.2024.12.015","DOIUrl":"https://doi.org/10.1016/j.jid.2024.12.015","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384618","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}
Nadia Shobnam, Grace Ratley, Sarini Saksena, Manoj Yadav, Prem Prashant Chaudhary, Ashleigh A Sun, Katherine N Howe, Manasi Gadkari, Luis M Franco, Sundar Ganesan, Katelyn J McCann, Amy P Hsu, Kishore Kanakabandi, Stacy Ricklefs, Justin Lack, Weiming Yu, Morgan Similuk, Magdalena A Walkiewicz, Donna D Gardner, Kelly Barta, Kathryn Tullos, Ian A Myles
{"title":"Topical Steroid Withdrawal Is a Targetable Excess of Mitochondrial NAD.","authors":"Nadia Shobnam, Grace Ratley, Sarini Saksena, Manoj Yadav, Prem Prashant Chaudhary, Ashleigh A Sun, Katherine N Howe, Manasi Gadkari, Luis M Franco, Sundar Ganesan, Katelyn J McCann, Amy P Hsu, Kishore Kanakabandi, Stacy Ricklefs, Justin Lack, Weiming Yu, Morgan Similuk, Magdalena A Walkiewicz, Donna D Gardner, Kelly Barta, Kathryn Tullos, Ian A Myles","doi":"10.1016/j.jid.2024.11.026","DOIUrl":"10.1016/j.jid.2024.11.026","url":null,"abstract":"<p><p>Topical steroid withdrawal (TSW) is a controversial diagnosis advocated by patients but often confused for atopic dermatitis. We conducted a multimodal pilot study of 16 patients fitting the TSW diagnostic profile, contrasting them against patients with atopic dermatitis (n = 10) and healthy controls (n = 11). Our clinical evaluations established objective diagnostic criteria that distinguish TSW from atopic dermatitis, metabolomics and transcriptomics of skin biopsies suggested that neuroinflammatory pathways are associated with complex I-mediated oxidation of NAD+, cellular and mouse models demonstrated that NAD+ metabolism was proinflammatory and glucocorticoid responsive, whereas functional assays demonstrated that the metabolic effects of glucocorticoids on the only cell type that aligns with the distribution and duration of TSW pathology could be mitigated by complex I blockade. These results informed a successful open-label trial using complex I-inhibiting interventions: metformin and berberine. Although this work represents a pilot study, to our knowledge, this work offers previously unreported mechanistic insights into TSW.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635046","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 Changing Landscape of Clinical Research in Pyoderma Gangrenosum.","authors":"Sarah L Becker, Alex G Ortega-Loayza","doi":"10.1016/j.jid.2024.12.023","DOIUrl":"https://doi.org/10.1016/j.jid.2024.12.023","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384617","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}