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

{"title":"Abundances but not concentrations of circulating unsaturated fatty acids are associated with incident psoriatic diseases: Evidence from cohort and Mendelian randomization studies","authors":"Minxue Shen ,&nbsp;Zhiwei Wang ,&nbsp;Danrong Jing ,&nbsp;Songchun Yang ,&nbsp;Yi Xiao ,&nbsp;Xiang Chen","doi":"10.1016/j.xjidi.2025.100437","DOIUrl":"10.1016/j.xjidi.2025.100437","url":null,"abstract":"<div><div>Whether the levels of circulating fatty acids (FAs) are associated with psoriasis and psoriatic arthritis remains unknown. To examine the measured and predicted levels of circulating FAs in association with incident psoriatic disease, 2-sample Mendelian randomization analysis was performed to examine the causal relationship between monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs) and psoriasis, and a cohort study of the UK Biobank participants was conducted to validate the findings, in terms of the measured and dietarily predicted levels of FAs. Mendelian randomization analysis identified a positive association of genetically predicted MUFAs% but inverse associations of PUFAs% and PUFAs/MUFAs with psoriasis and psoriatic arthritis. In the cohort, higher MUFAs% was associated with increased risks of psoriasis (relative risk = 1.109, <em>P</em> = .004) and psoriatic arthritis (relative risk = 1.188, <em>P</em> = .016), whereas higher PUFAs% and PUFAs/MUFAs were associated with lower risks of psoriasis (relative risk = 0.891, <em>P</em> = .001) and psoriatic arthritis (relative risk = 0.874, <em>P</em> = .051). Dietary scores that predict PUFAs% and MUFAs% showed consistent results with larger effect sizes. The effects of PUFAs% and MUFAs% were not significant in under- or normal-weighted participants. In conclusion, circulating PUFAs% and MUFAs% are causal factors for incident psoriatic diseases, and the effects might be modified by obesity.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 2","pages":"Article 100437"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145841217","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 standardized approach to test missense PNPLA1 rare genetic variants of uncertain significance in epidermal differentiation disorders","authors":"Nuria Pell ,&nbsp;Pauline Bernard ,&nbsp;Séverine Courrech ,&nbsp;Lukas Opalka ,&nbsp;Aina Millán-Sánchez ,&nbsp;Elise Levy ,&nbsp;Séverine Garnier ,&nbsp;Cyrielle Clément ,&nbsp;Pauline Le Faouder ,&nbsp;Katerina Vávrová ,&nbsp;Olga López ,&nbsp;Justine Bertrand-Michel ,&nbsp;Corinne Leprince ,&nbsp;Isabelle Fourquaux ,&nbsp;José-Enrique Mejia ,&nbsp;Jean-Christophe Pagès ,&nbsp;Juliette Mazereeuw-Hautier ,&nbsp;Nathalie Jonca","doi":"10.1016/j.xjidi.2025.100442","DOIUrl":"10.1016/j.xjidi.2025.100442","url":null,"abstract":"<div><div>Congenital ichthyoses, now renamed epidermal differentiation disorders (EDDs) (syndromic EDD or nonsyndromic EDD), are rare, disabling conditions caused by sequence variations in epidermal barrier genes. However, 5–10% of variants, called “variants of uncertain significance” (VUS), remain uncharacterized, and their pathogenicity is not demonstrated. We developed an approach for classifying VUS in nonsyndromic EDD associated with variant in <em>PNPLA1</em>. We generated <em>PNPLA1</em>-knockout human keratinocytes. PNPLA1, encoded by a missense VUS or by the reference coding sequence, was expressed after lentiviral transduction in the <em>PNPLA1</em>-knockout cells. Transduced cells were used to produce human epidermal equivalents, and the functionality of the normal or VUS-encoded proteins was evaluated. Compared with <em>PNPLA1</em>-knockout human epidermal equivalents re-expressing normal PNPLA1, <em>PNPLA1</em>-knockout human epidermal equivalents showed disrupted synthesis of ω-O-acylceramide, the normal product of PNPLA1, as well as abnormal vesicle-like structures and immature cornified envelopes, characteristic of the epidermis of patients with <em>PNPLA1</em> variants. Human epidermal equivalents expressing the <em>PNPLA1</em> VUS showed similar abnormalities, consistent with an impaired PNPLA1 function. This work demonstrated a feasible strategy to help reclassifying missense VUS, which can be extended to other EDD-related genes. Although further efforts are needed to translate this approach into clinical practice and help overcome current diagnostic limitations, such models are valuable tools for pathophysiological and preclinical research on EDDs.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 2","pages":"Article 100442"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037969","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":"Association of immune checkpoint inhibitor-induced bullous pemphigoid with underlying cancer type: A lack of association with cancer tissue COL17A1 mutations and dysregulation","authors":"Rachel C. Chang ,&nbsp;Henning Olbrich ,&nbsp;Yulu F. Wang ,&nbsp;Haley Gainer ,&nbsp;Nina Curkovic ,&nbsp;Theresa L. Walunas ,&nbsp;Jessica Shiu ,&nbsp;Parul Goyal ,&nbsp;Adrian P. Mansini ,&nbsp;Ralf J. Ludwig ,&nbsp;Kyle T. Amber","doi":"10.1016/j.xjidi.2026.100450","DOIUrl":"10.1016/j.xjidi.2026.100450","url":null,"abstract":"<div><div>Bullous pemphigoid (BP) is an autoimmune blistering disease caused by autoantibodies to collagen type 17 (<em>COL17A1</em>) and is a recognized immune-related adverse event in patients receiving immune checkpoint inhibitors (ICIs). We investigated whether cancer type influences the risk of developing ICI-induced BP and whether <em>COL17A1</em> mutations or dysregulation in tumor tissue contributes to disease-specific variation. Using TriNetX, systematic review, and bioinformatics datasets, we comprehensively assessed the associations of ICI-induced BP with different malignancy types as well as <em>COL17A1</em> gene expression, mutation frequency, and immune correlations across cancers. Lung cancer was the most common underlying malignancy in ICI-induced BP, but nonmelanoma skin cancer and renal cell carcinoma had the highest relative risk, whereas lung cancer had the lowest. ICI-induced BP was associated with improved survival across several cancers. Urothelial cancer showed the shortest time to onset, whereas renal cell carcinoma showed the longest. Cutaneous squamous cell carcinoma and melanoma exhibited the highest <em>COL17A1</em> mutation burden, whereas renal cell carcinoma had a low burden. <em>COL17A1</em> was overexpressed in several cancers but underexpressed in melanoma, without strong correlation to tumor-infiltrating immune cells. Although the incidence of ICI-induced BP significantly differed on the basis of cancer type, <em>COL17A1</em> mutations or dysregulation do not appear to drive this phenomenon, suggesting alternative immune mechanisms.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 2","pages":"Article 100450"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078087","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":"Human keratinocytes exhibit limited potential for SARS-CoV-2 infection despite ACE2 and mature cathepsin L expression","authors":"Leslie Hertereau ,&nbsp;Manon Barthe ,&nbsp;Noura Lamghari ,&nbsp;Peggy Merida ,&nbsp;Gaelle Pommier ,&nbsp;Elisabeth Pinel ,&nbsp;Jitendriya Swain ,&nbsp;Delphine Muriaux ,&nbsp;Hanan Osman-Ponchet ,&nbsp;Véronique M. Braud","doi":"10.1016/j.xjidi.2025.100447","DOIUrl":"10.1016/j.xjidi.2025.100447","url":null,"abstract":"<div><div>The distribution of receptors and cellular factors across tissues determines differential susceptibility of cells to viral infection. For severe acute respiratory syndrome coronavirus 2, viral spike and nucleocapsid proteins have been detected in the skin of infected patients. Whether the virus can directly infect skin cells has yet to be fully evaluated. Severe acute respiratory syndrome coronavirus 2 enters cells through 2 routes: ACE2-driven endocytosis and TMPRSS2-mediated plasma membrane fusion or ACE2/alternative receptors-driven endocytosis and cathepsin L–dependent fusion. This study assessed the gene and protein expression of these entry receptors and coreceptors in primary keratinocytes and fibroblasts. We found that the main severe acute respiratory syndrome coronavirus 2 receptor ACE2 is present in human keratinocytes and is upregulated during their differentiation and toll-like receptor 3–mediated activation, whereas the coreceptor TMPRSS2 for fusion is absent, but mature cathepsin L is expressed. In vitro infection assays using the severe acute respiratory syndrome coronavirus 2 Delta variant showed that the virus can bind to the cell surface but cannot replicate within the cells. These findings suggest that although active viral replication in keratinocytes is unlikely, the presence and inducible upregulation of ACE2 in response to inflammatory stimuli may confer a limited potential for cutaneous viral entry, warranting further investigation into the consequences in terms of local inflammation and viral transmission.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 2","pages":"Article 100447"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037970","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":"Spatiotemporal fluorescence imaging of microRNA activity in 3-D models of human epidermis reveals contribution of the Notch pathway in the regulation of miR-30a in aging skin","authors":"Alejandro Gonzalez Torres ,&nbsp;Fabien P. Chevalier ,&nbsp;Ruth Aquino ,&nbsp;Mélanie Aimard ,&nbsp;Patrick Baril ,&nbsp;Jérôme Lamartine","doi":"10.1016/j.xjidi.2025.100444","DOIUrl":"10.1016/j.xjidi.2025.100444","url":null,"abstract":"<div><div>MicroRNAs are short noncoding RNAs that play important roles in fine tuning genetic networks as genes post-transcriptional regulators. Monitoring the regulatory activity of microRNAs is technically challenging, especially in primary cells and 3-dimensional (3D) organotypic cultures. We optimized the previously reported RILES miRNA-ON sensor system to visualize the spatial expression of miR-203 and miR-30a by fluorescence imaging in 2-dimensional and 3D cultures of human primary keratinocytes. The generated system, called RIFES (RNAi-inducible fluorescence expression system), successfully imaged the expression of miR-30a-5p and miR-30a-3p in the suprabasal layers of the epidermis. This information was exploited to uncover the molecular mechanisms regulating the expression of miR-30a in human keratinocytes. We demonstrate that chemical inhibition of the Notch1 pathway induced GFP expression in undifferentiated RIFES/miR-30a keratinocyte cells, with fluorescence redistribution in the basal layers of 3D RIFES/miR-30a epidermis. Moreover, overexpressing miR-30a in 3D epidermal models resulted in NOTCH1 downregulation, suggesting a negative feedback loop between miR-30a and Notch. Because the Notch pathway was found downregulated in aged epidermis biopsies, we propose that Notch downregulation contributes to miR-30a induction during aging. Therefore, the RIFES system appears as a powerful tool to visualize the expression of microRNAs in 3D epidermis and to identify their potential upstream regulators.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 2","pages":"Article 100444"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977631","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":"Assessing public interest in artificial intelligence in dermatology: A Google Trends analysis","authors":"Matthew J. Yan BS, BA ,&nbsp;Yuan Chun Jiang BS ,&nbsp;Shannon Wongvibulsin MD, PhD ,&nbsp;Steven T. Chen MD, MPH, MS-HPEd","doi":"10.1016/j.xjidi.2025.100435","DOIUrl":"10.1016/j.xjidi.2025.100435","url":null,"abstract":"<div><div>Artificial intelligence (AI) is rapidly transforming dermatology, particularly through diagnostic imaging and enhancing patient management. Despite expanding clinical applications, public engagement with AI in dermatology remains underexplored. This study addresses this gap by analyzing public interest in AI dermatology over the past decade using Google Trends. Search terms were categorized into groups of “AI dermatology,” “general AI,” “AI nondermatology,” “general dermatology,” and “general nondermatology.” Monthly Search Volume Index values from January 2015 to January 2025 were collected, and linear and exponential regression models quantified temporal trends. Geographic analysis evaluated the frequency of countries appearing in the top five search volumes for each term. Public interest in AI dermatology terms increased markedly after 2022, with growth of 73.6%, 143.6%, and 59.1% in 2022, 2023, and 2024, respectively. AI dermatology terms demonstrated a steeper linear slope (6.212) compared with general AI (6.181) and dermatology terms (1.61), and an exponential growth factor of 0.551. Interest was highest in Singapore, Ireland, Australia, the Philippines, New Zealand, and the United Arab Emirates. These findings indicate a substantial rise in global engagement with AI in dermatology and highlight the importance of integrating public interest considerations into AI tool development, clinical practice, patient safety, and equitable access.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 2","pages":"Article 100435"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798247","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":"Spatially controlled induction and regression of basal cell carcinoma, visualized by serial imaging in young and old mice","authors":"Elisabeth A. Pedersen ,&nbsp;Marina Grachtchouk ,&nbsp;Paul W. Harms ,&nbsp;Allison K.C. Furgal ,&nbsp;Dawn Wilbert ,&nbsp;Allesandra Hoover ,&nbsp;Daryna V. Hodgson ,&nbsp;Katelyn Fiehler ,&nbsp;Anissa Alam ,&nbsp;Nihal Lingam ,&nbsp;Sunny Y. Wong ,&nbsp;Monique E. Verhaegen ,&nbsp;Andrzej A. Dlugosz","doi":"10.1016/j.xjidi.2025.100441","DOIUrl":"10.1016/j.xjidi.2025.100441","url":null,"abstract":"<div><div>Basal cell carcinoma (BCC) is the most common skin malignancy, and the risk of developing BCC increases with age. BCC results from dysregulated Hedgehog signaling leading to activation of GLI transcription factors. In this study, we examined the impact of aging on BCC in cohorts of young (n = 37) versus aged (n = 97) mice using a transgenic mouse model in which GLI2A (GLI2 activator) was induced in mice at either the age of 7 weeks or 22–24 months, and BCC tumor development was monitored by weekly imaging. Young mice developed tumors slightly sooner and in greater numbers than aged mice but demonstrated similar growth rates once tumors appeared. However, BCC-associated increases in blood vessel diameter, tortuosity, and ulceration were impacted by age. BCCs in both young and aged mice underwent similarly rapid regression after GLI2A transgene inactivation. Taken together, our findings reveal that aging affects tumor-associated vasculature but not BCC formation or regression in our model. These results are in keeping with the notion that a major contributor to the increased incidence of BCCs in elderly patients is the accumulation of oncogenic driver mutations over time rather than intrinsic changes in aged skin that promote BCC tumorigenesis.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 2","pages":"Article 100441"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939041","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":"Diabetes status is associated with greater disease severity in hidradenitis suppurativa","authors":"Negar Foolad ,&nbsp;Amy J. Petty ,&nbsp;Winston Liu ,&nbsp;Jeffery T. Kwock ,&nbsp;Beiyu Liu ,&nbsp;Cynthia L. Green ,&nbsp;Andrea D. Coviello ,&nbsp;Tarannum Jaleel","doi":"10.1016/j.xjidi.2025.100439","DOIUrl":"10.1016/j.xjidi.2025.100439","url":null,"abstract":"<div><div>With the rising prevalence of endocrine conditions in the U.S., it is important to examine the relationship between diabetes mellitus and hidradenitis suppurativa (HS) severity. This retrospective, cross-sectional study evaluated whether diabetes status and HbA1c levels are associated with HS severity among 275 physician-diagnosed patients seen at an HS Specialty Clinic between June 2016 and January 2021. The primary outcome was HS severity measured by the International HS Severity Score System (IHS4); the secondary outcome was pain severity measured by the Numeric Pain Rating Scale (NRS).Among participants, 44.3% were non-diabetic, 35.3% pre-diabetic, and 20.4% diabetic. Median HbA1c levels were lowest in non-diabetic patients (5.3 [5.1, 5.5]) and highest in diabetic patients (6.9 [6.3, 8.4]). The NRS pain score was also highest in the diabetic cohort (5.0 [0.0–8.0]) compared to the non-diabetic (2.0 [0.0–5.0]) and pre-diabetic (4.0 [0.0–6.0]) groups (<em>p</em> = .005). A significant association was observed between HbA1c and IHS4 in univariate analysis (<em>p</em> = .004), with multivariable analysis approaching significance (<em>p</em> = .053) after adjusting for covariates. These findings suggest diabetes and higher HbA1c levels correlate with increased HS severity and pain. Prevention and management of diabetes may therefore modify the clinical course of HS.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 2","pages":"Article 100439"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396182","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":"Increased Risk of Postoperative Complications in Patients with Hypertension Undergoing Mohs Micrographic Surgery","authors":"Alexandra Elder ,&nbsp;Henry Y. Yang ,&nbsp;Megan O’Donnell-Cappelli ,&nbsp;Jenna L. Mandel ,&nbsp;Molly Wallace ,&nbsp;Lauren Banner ,&nbsp;Ramsay Hafer ,&nbsp;Thomas Z. Rohan ,&nbsp;Neda Nikbakht","doi":"10.1016/j.xjidi.2025.100414","DOIUrl":"10.1016/j.xjidi.2025.100414","url":null,"abstract":"<div><div>Hypertension has been previously associated with higher intraoperative bleeding risk in patients undergoing Mohs micrographic surgery. However, the risks of common postoperative Mohs micrographic surgery complications have not been substantiated by large studies. Our study aimed to assess the risks of common Mohs micrographic surgery complications for patients with hypertension utilizing the TriNetX database, a global health records database encompassing over 105 million patients’ data, from January 2009 to January 2024. After 1:1 propensity score matching for age, sex, race, diabetes, nicotine dependence, obesity, and anticoagulant use, the final analysis included 80,739 patients in each cohort of patients with hypertension and matched controls. We found that within a 60-day postoperative period, patients with hypertension had a significantly higher risk of bleeding both intraoperatively (OR = 2.19, 95% confidence interval = 1.39–3.46) and postoperatively (OR = 2.11, 95% confidence interval = 1.44–3.09). In addition, patients with hypertension faced a significantly higher risk of various postoperative infections such as gangrene (OR = 2.17, 95% confidence interval = 1.24–3.79) and impaired wound healing (OR = 1.25, 95% confidence interval = 1.06–1.48). Results did not vary significantly by stage of hypertension. Essential hypertension is associated with significantly increased intraoperative and postoperative hemorrhage, infections, and wound disruptions; thus, it may be beneficial to assess and risk stratify patients with hypertension before performing Mohs micrographic surgery.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100414"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145322958","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":"Mucosal-Associated Invariant T (MAIT) Cells in Skin Immunity: Metabolic Regulation, Tissue Adaptation, and Roles in Skin Inflammation and Disease","authors":"Namya Nanda ,&nbsp;Chloe Kim ,&nbsp;Ishita Jain ,&nbsp;Charlene Cai ,&nbsp;Martin P. Alphonse","doi":"10.1016/j.xjidi.2025.100425","DOIUrl":"10.1016/j.xjidi.2025.100425","url":null,"abstract":"<div><div>Mucosal-associated invariant T (MAIT) cells are a unique subset of innate-like T lymphocytes that recognize microbial-derived vitamin B metabolites presented by the nonpolymorphic MR1 (major histocompatibility complex class I–related protein). These cells comprise about 1–10% of circulating T cells in humans and are abundant at mucosal surfaces, including the skin. MAIT cells possess a semi-invariant TCR (typically, TRAV1-2/TRAJ33 in humans) and can be activated by riboflavin metabolites such as 5-OP-RU (5-[2-oxopropylideneamino]-6-d-ribitylaminouracil) and 5-OE-RU (5-2-oxoethylideneamino]-6-d-ribitylaminouracil) as well as through cytokine-mediated pathways independent of MR1. Upon activation, MAIT cells quickly produce proinflammatory cytokines, including IFN-γ, TNF-α, and IL-17, and perform cytotoxic functions by releasing granzyme B and perforin. This review thoroughly explores the role of MAIT cells in skin immunity and skin diseases. We detail their involvement in inflammatory skin conditions such as psoriasis, atopic dermatitis, and hidradenitis suppurativa, where alterations in MAIT cell numbers and functions have been observed. The review also addresses MAIT cells’ roles in wound healing, tissue repair, and antimicrobial defense within the skin. Furthermore, we evaluate the potential of targeting MAIT cells for therapy, including how current treatments affect them and the development of new immunometabolic strategies. Gaining a better understanding of MAIT cell biology in skin contexts could provide new insights into the development of skin diseases and lead to innovative dermatological treatments.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100425"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571759","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}