Mucosal Immunology最新文献

{"title":"Single-cell RNA profiling identifies immune cell population shifts in diabetes associated mucosal inflammation.","authors":"Bushra Alghamdi, Min Liu, Xin Huang, Rahul Debnath, Hamideh Afzali, Michael Troka, Akira Hasuike, Quinn Easter, Mi Zhou, Kevin Byrd, Michael Gonzalez, Kang I Ko, Dana T Graves","doi":"10.1016/j.mucimm.2025.06.008","DOIUrl":"10.1016/j.mucimm.2025.06.008","url":null,"abstract":"<p><p>Poorly controlled diabetes significantly worsens periodontal disease, affecting millions worldwide, yet the mechanisms driving this destructive synergy remain unclear. We generated single-cell RNA sequencing profiles of diabetic periodontal tissue, revealing increased γ^δ T-cells, a loss of Tregs and greater neutrophil polarization as key mediators of diabetes-enhanced periodontitis. Flow cytometry confirmed significant expansion of IL-17A⁺ γ^δ+ T-cells and reduced Tregs in diabetic mice, with parallel findings of elevated CD3⁺IL-17A⁺ cells and reduced Tregs in human diabetic periodontal specimens. scRNAseq determined that diabetes caused a global increase in pro-inflammatory and a decrease in pro-resolving transcripts and enhanced inflammatory neutrophil polarization. Selective γ^δ T-cell inhibition reversed diabetes-enhanced periodontal destruction while minimally affecting normoglycemic controls and returned neutrophil infiltration to normoglycemic levels. These findings point to unique aspects of diabetes-induced dysregulation, and implicate γ^δ T-cells as a driving factor and point to them as a potential therapeutic target in periodontitis and other diabetic complications.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exogenous ephrin-A3 reverses loss of vaginal epithelial barrier protection in progestin-treated mice.","authors":"Mohan Liu, Rodolfo D Vicetti Miguel, Kristen Aceves, Thomas L Cherpes","doi":"10.1016/j.mucimm.2025.06.007","DOIUrl":"10.1016/j.mucimm.2025.06.007","url":null,"abstract":"<p><p>Desmosomes are junctional complexes that confer mechanical strength and enhance barrier protection at mucosal epithelial surfaces by anchoring intermediate filaments to plasma membrane. These roles are best defined in cutaneous epithelium, but we previously identified lower levels of the desmosomal cadherins desmoglein-1 (DSG1) and desmocollin-1 (DSC1) and loss of barrier function in vaginal epithelium of mice treated systemically with the progestin depot medroxyprogesterone acetate (DMPA). We also showed these changes were avoided in mice treated with both DMPA and a conjugated equine estrogen vaginal cream. We extend these earlier results in the current investigation, identifying ephrin-A3 (EFNA3) as an important regulator of desmosomal cadherin gene expression in murine vaginal epithelial tissue. Moreover, topical treatment of mice with recombinant EFNA3 (rEFNA3) significantly increased vaginal expression of DSG1 and partially reversed the loss of vaginal epithelial barrier function induced by DMPA treatment. Consistent with this improvement in vaginal epithelial barrier protection, mortality caused by genital herpes simplex virus type 2 infection was delayed, but not prevented, in mice administered DMPA and rEFNA3 vs. DMPA alone. Together, current studies identify EFNA3 as a key regulator of desmosomal structure and function in vaginal epithelium and newly suggest that ephrin-Eph signaling pathways will provide an important target for enhancing vaginal epithelial integrity and barrier function.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memory T cell formation and phenotype varies across intestinal compartments.","authors":"Sarah Sandford, Maximilien Evrard, Thomas N Burn, Susan N Christo, Marina H Yakou, Andreas Obers, Yannick O Alexandre, Laura K Mackay, Scott N Mueller","doi":"10.1016/j.mucimm.2025.06.005","DOIUrl":"10.1016/j.mucimm.2025.06.005","url":null,"abstract":"<p><p>Numerous studies have shown that tissue-resident memory T (T_RM) cells form in the intestine following pathogen clearance. However, most knowledge of intestinal T_RM cells has derived from analyses restricted to the small intestine (SI). In contrast, less is known about T_RM cell formation in the large intestine (LI). Here, we compared the abundance and phenotype of memory T cells across intestinal compartments. Using mouse models of infection, we observed that fewer memory T cells formed in the LI compared to the SI. Moreover, we found that T cells in the epithelium and lamina propria of the LI colon and caecum were phenotypically distinct from SI counterparts, comprising Ly6C-expressing CD8⁺ T_RM cells with a distinct cytokine and granzyme profile. Using both loss- and gain-of-function approaches, we identified site-specific TGF-β dependencies, whereby Ly6C⁺CD103^- T_RM cells developed independently of TGF-β in both the SI and LI. In contrast, augmenting TGF-β signalling preferentially expanded Ly6C^-T_RMpopulations in the LI but not the SI, indicating that TGF-β signalling drives T_RMcell heterogeneity between these compartments. Together, these findings underscore how regional differences in T_RM cell responsiveness to local cues shape their development, phenotype, and function along the gastrointestinal tract.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental inflammation-driven T cell memory formation promotes allergic responses in offspring via endogenous glucocorticoids.","authors":"Myoung Seung Kwon, Won Hyung Park, Jeongwoo La, Chae Won Kim, Heung Kyu Lee","doi":"10.1016/j.mucimm.2025.06.006","DOIUrl":"10.1016/j.mucimm.2025.06.006","url":null,"abstract":"<p><p>Maternal exposure to environmental change during pregnancy is a critical determinant of offspring health and disease. Previous epidemiological studies have reported that maternal inflammation is linked to an increased incidence of postnatal allergy in offspring, although the underlying mechanisms remain largely unexplored. In this study, we employed a lipopolysaccharide-induced maternal inflammation murine model and found that offspring from dams with maternal immune activation (MIA) exhibited heightened allergic responses to house dust mite allergen. MIA offspring showed an increase in CD4⁺ T cell responses, which were mediated by increased T cell survival after activation, leading to promoting central and resident memory T cells formation. During maternal inflammation, TNF-α was identified as a crucial cytokine driving the heightened allergic response in offspring. TNF-α activates placental neutrophil, leading to placental necrosis. In parallel with placental damage, MIA offspring demonstrated increased glucocorticoid secretion in response to stress. Blockade of the glucocorticoid pathway during the sensitization phase mitigated the enhanced T cell memory response in MIA offspring, highlighting a mechanism by which maternal inflammation potentially modulates immune responses in offspring. Our findings elucidate one of the pathways by which maternal inflammation can influence postnatal immune regulation in offspring.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immunity of the gut epithelium: Blowing in the WNT?","authors":"Maaike H de Vries, Ewart W Kuijk, Edward E S Nieuwenhuis","doi":"10.1016/j.mucimm.2025.06.004","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.06.004","url":null,"abstract":"<p><p>Intestinal epithelial cells need to be able to launch a quick and adequate immune response against pathogens, while tolerating commensals. This delicate balance requires a tight control over the activation of the NFκB and Interferon pathways to prevent chronic inflammation. Simultaneously, intestinal stem cell maintenance and differentiation are strictly regulated by the WNT/β-catenin and Bone Morphogenetic Protein signaling pathways to allow proper tissue homeostasis. There is emerging evidence that these cell identity and innate immunity pathways are molecularly intertwined, which may have implications for our mechanistic understanding of intestinal diseases such as inflammatory bowel disease and colorectal cancer. Here, we provide a comprehensive overview of the most important molecular interactions between these pathways. We identify the current gaps in our knowledge, and we propose promising areas for future research, in particular organoid research combined with single cell sequencing technologies.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysbiosis of the gut microbiome may contribute to the pathogenesis of oral lichen planus through Treg dysregulation.","authors":"Shiho Yokomizo, Naoki Kaneko, Hu Chen, Lijing Yan, Shoji Tsuji, Shohei Akagawa, Junsei Sameshima, Tomoki Sueyoshi, Haruki Nagano, Yuka Miyahara, Yasuhisa Kamikaseda, Hajime Kido, Yoshikazu Hayashi, Masaki Yamauchi, Tamotsu Kiyoshima, Yuichi Goto, Yukiko Ohyama, Kazunari Kaneko, Masafumi Moriyama, Shintaro Kawano","doi":"10.1016/j.mucimm.2025.05.009","DOIUrl":"10.1016/j.mucimm.2025.05.009","url":null,"abstract":"<p><p>Oral lichen planus (OLP) is a chronic inflammatory disorder with autoimmune features and malignant transformation risk, lacking a definitive treatment, with CD4⁺ T cells being pivotal in its pathogenesis. Dysbiosis, an imbalance in the microbiome, is linked to various autoimmune and inflammatory diseases, where CD4⁺ T cells play a significant role. Given these insights, the development of OLP might be influenced by dysbiosis. This study investigates the association between dysbiosis and CD4⁺ T cells in OLP. We collected stool and saliva samples from OLP patients, conducting 16S rRNA gene analysis and mass spectrometry, and assessed CD4⁺ T cell characteristics in lesions through multiplex immunofluorescence and single-cell RNA sequencing. Peripheral blood samples were subjected to flow cytometry and cell culture assays. Results showed extensive gut dysbiosis in OLP patients, notably a reduction in short-chain fatty acid (SCFA)-producing bacteria essential for regulatory T cell (Treg) differentiation. While various CD4⁺ T cell subsets, including Tregs, were present in tissues, these Tregs as unresponsive to specific antigens, showing reduced immunosuppressive molecule expression. The decline in SCFA-producing bacteria correlated with fewer activated Tregs in tissues and blood. These findings suggest that gut dysbiosis may contribute to OLP by impairing Treg regulation, influencing disease pathogenesis.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated enema administration in rhesus macaques is not sufficient to promote bacterial dysbiosis or gastrointestinal dysfunction.","authors":"Alexandra M Ortiz, Fabiola Castello Casta, Elizabeth G Bodykevich, Jacob K Flynn, Christine M Fennessey, Kelsie Brooks, Delmy Ruiz, Debra S Yee, Jennifer Simpson, Andrew R Rahmberg, Brandon F Keele, Jason M Brenchley","doi":"10.1016/j.mucimm.2025.06.002","DOIUrl":"10.1016/j.mucimm.2025.06.002","url":null,"abstract":"<p><p>Chronic gastrointestinal diseases are a significant global health burden that can require the use of gastrointestinal-cleansing regimens for diagnostics or therapeutic treatment. These regimens are beneficial for facilitating surgical preparation, drug delivery, colorectal cancer screenings, and personal use is common among proponents of natural health and among certain populations at high risk of HIV acquisition. It remains unclear, however, whether repeated clearance of the colonic microbiome induces persistent changes in the microbiome, intestinal immunity, and viral disease susceptibility. We addressed these parameters by repeatedly administering iso-osmolar enemas to rhesus macaques prior to low-dose intra-rectal challenge with simian immunodeficiency virus (SIV). Considering both longitudinal and cross-sectional analyses, we observed no consistent changes in the fecal microbiome or intestinal immune parameters of treated animals, nor were significant differences observed in susceptibility to SIV acquisition. Unexpectedly, enema-treated animals exhibited significantly lower setpoint viral loads after infection, although we were unable to clearly identify attributing causes. Our study demonstrates that repeated microbiome clearance using clinically administered iso-osmolar enemas is not sufficient to restructure the fecal microbiome, perturb intestinal immune parameters, or increase susceptibility to mucosal SIV challenge. This research framework serves as a model for the development of colonic-administered diagnostics and interventions.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editing B cells at the IGHA2 gene position provides alternative route to therapeutic IgA production.","authors":"Marine Cahen, Jenny Léonard, Ophélie Dézé, Laurent Deleurme, Maiwenn Pineau, Anne-Laure Tanguy, Stéphane Paul, Jérome Moreaux, Grégory Noël, Natsuko Ueda, Yannic Danger, Michel Cogné","doi":"10.1016/j.mucimm.2025.06.001","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.06.001","url":null,"abstract":"<p><p>As professional and long-lived immunoglobulin (Ig) producers, B cells represent attractive candidates for adoptive immunotherapy and their highly expressed Ig heavy (IgH) chain locus is ideal for editing. Each of its constant genes, expressed after class switch recombination (CSR), affords an attractive platform where an adoptive Ig variable domain would acquire IgM, IgG, IgE or IgA class-specific functions. In particular, IgA plays a unique role in mucosal immunity but has remained excluded from therapeutic applicability due to unfavorable chemistry, manufacturing, and control (CMC) issues. To test whether these barriers could be overcome by producing IgA in vivo rather than in vitro, we edited the human B cell-specific IGHA2 gene and found it to be a suitable platform for inserting gene cassettes for expression in B cells. Targeted deletions can also induce CSR to IgA2, while, by combining IgA2 CSR with the insertion of a linked VH and a complete light chain, we have replaced the endogenous Ig chains with a customized full-size but single-chain IgA carrying an adoptive antigen specificity. Taken together, we show that IGHA2-editing of B cells could provide a novel avenue to B-cell targeted delivery of therapeutic IgA, overcoming the problems that have so far excluded IgA from clinical use.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifelong partners: Gut microbiota-immune cell interactions from infancy to old age","authors":"Julia A. Brown ,&nbsp;Hilal Bashir ,&nbsp;Melody Y. Zeng","doi":"10.1016/j.mucimm.2025.01.006","DOIUrl":"10.1016/j.mucimm.2025.01.006","url":null,"abstract":"<div><div>Our immune system and gut microbiota are intricately coupled from birth, both going through maturation during early life and senescence during aging almost in a synchronized fashion. The symbiotic relationship between the human host and microbiota is critically dependent on a healthy immune system to keep our microbiota in check, while the microbiota provides essential functions to promote the development and fitness of our immune system. The partnership between our immune system and microbiota is particularly important during early life, when microbial ligands and metabolites shape the development of the immune cells and immune tolerance; during aging, having sufficient beneficial gut bacteria is critical for the maintenance of intact mucosal barriers, immune metabolic fitness, and strong immunity against pathogens. The immune system during childhood is programmed, with the support of the microbiota, to develop robust immune tolerance, and limit autoimmunity and metabolic dysregulation, which are prevalent during aging. This review comprehensively explores the mechanistic underpinnings of gut microbiota-immune cell interactions during infancy and old age, with the goal to gain a better understanding of potential strategies to leverage the gut microbiota to combat age-related immune decline.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 509-523"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronological maturation of the skin immune barrier is topographically different","authors":"Anikó Kapitány ,&nbsp;Lilla Soltész ,&nbsp;Vivien Stercel ,&nbsp;Lilla Szabó ,&nbsp;Orsolya Somogyi ,&nbsp;Eszter Anna Janka ,&nbsp;Viktória Nagy ,&nbsp;Szilárd Póliska ,&nbsp;Krisztián Gáspár ,&nbsp;Zoltán Hendrik ,&nbsp;Dániel Törőcsik ,&nbsp;Zsolt Dajnoki ,&nbsp;Andrea Szegedi","doi":"10.1016/j.mucimm.2025.03.004","DOIUrl":"10.1016/j.mucimm.2025.03.004","url":null,"abstract":"<div><div>Adult skin varies across regions, with differences in chemical, physical, microbiota, and immune barriers. However, data on topographical immune differences in other age groups are limited. This study aimed to explore the chronological maturation of the immune barrier in various skin regions.</div><div>A TaqMan low-density array and immunohistochemical and immunofluorescence detection of various immune cells and mediators in sebaceous gland-rich (SGR) and gland-poor (GP) healthy skin were performed in children, adolescents, and adults.</div><div>The maturation of SGR skin showed a general upward trend in the mRNA levels of most Th17-related molecules with a significant increase in IL-1B from childhood to adulthood, but with only a slight elevation between childhood and adolescence. In addition, T cell, Treg, dendritic cell (DC) counts, as well as the levels of several Th17-related proteins (IL-17, IL-10, IL-23, CCL20, S100A8, sfTSLP, LCN2), increased significantly with age. In GP skin, AHR mRNA levels decreased, while Th17-related protein levels increased, although only moderately. When comparing the two regions, SGR and GP skin were similar in childhood, with differences emerging in adolescence and becoming significant in adulthood, particularly in the IL-17 pathway, mainly produced by Th17 cells.</div><div>Our results show a similarly directed maturation process in GP and SGR regions, with more pronounced development of the SGR skin immune barrier (with more immune cell infiltration and cytokine production) during and after the adolescence. This is likely to be related to the significant changes in the chemical and microbiota barriers of the SGR skin during adolescence, and may explain the high incidence of inflammatory skin diseases on the SGR skin of adolescents, highlighting the need for targeted skin care in this region.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 730-741"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}