Mucosal Immunology最新文献

{"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}

{"title":"Lung-resident memory Th2 cells regulate pulmonary cryptococcosis by inducing type-II granuloma formation","authors":"Keigo Ueno ,&nbsp;Akiko Nagamori ,&nbsp;Nahoko Oniyama Honkyu ,&nbsp;Kyung J. Kwon-Chung ,&nbsp;Yoshitsugu Miyazaki","doi":"10.1016/j.mucimm.2025.02.004","DOIUrl":"10.1016/j.mucimm.2025.02.004","url":null,"abstract":"<div><div>Lung-resident memory T cells (lung TRMs) settle in the lung and respond rapidly to external antigens, and are therefore considered to have great potential for development of respiratory vaccines. Here, we demonstrate that lung-resident memory Th2 cells (lung TRM2) protect against pulmonary mycosis caused by <em>Cryptococcus gattii</em>. We developed novel whole-cell intranasal vaccines using a heat-inactivated <em>C.<!--> <!-->gattii</em> capsule-deficient strain <em>cap59</em>Δ, which induced ST-2⁺ Gata-3⁺ lung TRM2 specifically responding to <em>C.<!--> <!-->gattii</em> whole-cell antigen. Lung fungal burden and survival rate were significantly improved in immunized mice after infection challenge. The immunosuppressive agent FTY720 did not impact vaccine effectiveness, and adoptive transfer of lung TRMs into Rag-1-deficient mice decreased the lung fungal burden. In IL-4/IL-13 double-knockout (DKO) mice, immunization did not efficiently induce eosinophil recruitment and granuloma formation, and the fungal burden was not decreased after infection challenge. Co-culture of lung TRM2 with myeloid lineages induced multinucleated giant cells (MGCs) in the presence of antigen, which phagocytosed live <em>C.<!--> <!-->gattii</em> cells without opsonization, whereas lung TRM2 from DKO mice did not induce MGCs. These findings provide a new model in which lung TRM2 suppress <em>C.<!--> <!-->gattii</em> infection via granuloma induction.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 631-642"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472230","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":"Interleukin-10 production by innate lymphoid cells restricts intestinal inflammation in mice","authors":"Jing Li ,&nbsp;Justin Jacobse ,&nbsp;Jennifer M. Pilat ,&nbsp;Harsimran Kaur ,&nbsp;Weihong Gu ,&nbsp;Seung Woo Kang ,&nbsp;Mark Rusznak ,&nbsp;Hsin-I Huang ,&nbsp;Julio Barrera ,&nbsp;Pauline A. Oloo ,&nbsp;Joseph T. Roland ,&nbsp;Caroline V. Hawkins ,&nbsp;Andrew P. Pahnke ,&nbsp;Marian Khalil ,&nbsp;M.Kay Washington ,&nbsp;Keith T. Wilson ,&nbsp;Christopher S. Williams ,&nbsp;R.Stokes Peebles Jr ,&nbsp;Liza Konnikova ,&nbsp;Yash A. Choksi ,&nbsp;Jeremy A. Goettel","doi":"10.1016/j.mucimm.2025.02.005","DOIUrl":"10.1016/j.mucimm.2025.02.005","url":null,"abstract":"<div><div>Interleukin-10 (IL-10) is an immunomodulatory cytokine critical for intestinal immune homeostasis. IL-10 is produced by various immune cells but IL-10 receptor signaling in intestinal CX₃CR1⁺ mononuclear phagocytes is necessary to prevent spontaneous colitis in mice. Here, we utilized fluorescent protein reporters and cell-specific targeting and found that <em>Rorc</em>-expressing innate lymphoid cells (ILCs) produce IL-10 in response to anti-CD40-mediated intestinal inflammation. Deletion of <em>Il10</em> specifically in <em>Rorc</em>-expressing ILCs led to phenotypic changes in intestinal macrophages and exacerbated both innate and adaptive immune-mediated models of experimental colitis. The population of IL-10⁺ producing ILCs shared markers with both ILC2 and ILC3 with nearly all ILC3s being of the NCR⁺ subtype. Interestingly, <em>Ccl26</em> was enriched in IL-10⁺ ILCs and was markedly reduced in IL-10-deficient ILC3s. Since CCL26 is a ligand for CX₃CR1, we employed RNA <em>in situ</em> hybridization and observed increased numbers of ILCs in close proximity to <em>Cx3cr1</em>-expressing cells under inflammatory conditions. Finally, we generated transgenic <em>Rorc</em>^tdTomato reporter mice that faithfully marked RORγt⁺ cells that could rescue disease pathology and aberrant macrophage phenotype following adoptive transfer into mice with selective <em>Il10</em> deficiency in ILC3s. These results demonstrate that IL-10 production by a population of ILCs functions to promote immune homeostasis in the intestine possibly via direct effects on intestinal macrophages.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 643-655"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483613","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":"Immune crosstalk between respiratory and intestinal mucosal tissues in respiratory infections","authors":"Min Zhao ,&nbsp;Lei Zhou ,&nbsp;Shuo Wang","doi":"10.1016/j.mucimm.2024.12.013","DOIUrl":"10.1016/j.mucimm.2024.12.013","url":null,"abstract":"<div><div>Mucosal tissues, including those in the respiratory and gastrointestinal tracts, are critical barrier surfaces for pathogen invasion. Infections at these sites not only trigger local immune response, but also recruit immune cells from other tissues. Emerging evidence in the mouse models and human samples indicates that the immune crosstalk between the lung and gut critically impacts and determines the course of respiratory disease. Here we summarize the current knowledge of the immune crosstalk between the respiratory and gastrointestinal tracts, and discuss how immune cells are recruited and migrate between these tissues during respiratory infections. We also discuss how commensal bacteria contribute to these processes.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 501-508"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927532","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":"Triggering mouth-resident antiviral CD8+ T cells potentiates experimental periodontitis","authors":"Flávia M. Saavedra ,&nbsp;Danielle B. Brotto ,&nbsp;Vineet Joag ,&nbsp;Courtney A. Matson ,&nbsp;Pavel P. Nesmiyanov ,&nbsp;Mark C. Herzberg ,&nbsp;Vaiva Vezys ,&nbsp;David Masopust ,&nbsp;J. Michael Stolley","doi":"10.1016/j.mucimm.2025.02.003","DOIUrl":"10.1016/j.mucimm.2025.02.003","url":null,"abstract":"<div><div>Emerging evidence indicates that gingival-resident helper CD4⁺ T cells are major drivers of periodontal inflammation in response to commensal and pathogenic oral microorganisms. Whether tissue-resident memory CD8⁺ T cells (T_RM), which principally safeguard against viruses and cancer but also drive certain autoimmune and inflammatory conditions, impact periodontitis progression and severity remain unknown. We asked whether local reactivation of oral CD8⁺ T_RM of a defined antigen specificity could exacerbate ligature-induced periodontitis (LIP), a well-established model of periodontal disease in mice. Topical application of virus-mimicking peptides to the oral mucosa concurrent with LIP 1) intensified alveolar bone loss, 2) amplified gingival and cervical lymph node inflammation, and 3) stimulated gingival transcriptional changes in genes related to innate immune sensing and cell-mediated cytotoxicity. Therapeutic depletion of CD103-expressing oral CD8⁺ T_RM in advance of LIP prevented exacerbation of disease. These observations provide evidence that oral CD103⁺ CD8⁺ T_RM have the potential to participate in gingival inflammation, alveolar bone loss, and periodontitis.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 620-630"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483673","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":"Female sex hormones and the oral contraceptive pill modulate asthma severity through GLUT-1","authors":"Alexandra C. Brown ,&nbsp;Olivia R. Carroll ,&nbsp;Jemma R. Mayall ,&nbsp;Nazanin Zounemat-Kermani ,&nbsp;Samantha L.E. Vinzenz ,&nbsp;Henry M. Gomez ,&nbsp;Ed F. Mills ,&nbsp;Richard Y. Kim ,&nbsp;Chantal Donovan ,&nbsp;Katherine J. Baines ,&nbsp;Evan J. Williams ,&nbsp;Bronwyn S. Berthon ,&nbsp;Katie Wynne ,&nbsp;Hayley A. Scott ,&nbsp;James W. Pinkerton ,&nbsp;Yike Guo ,&nbsp;Philip M. Hansbro ,&nbsp;Paul S. Foster ,&nbsp;Peter A.B. Wark ,&nbsp;Sven-Erik Dahlen ,&nbsp;Jay C. Horvat","doi":"10.1016/j.mucimm.2025.02.006","DOIUrl":"10.1016/j.mucimm.2025.02.006","url":null,"abstract":"<div><div>Females are disproportionately affected by asthma. An increased understanding of how female sex hormones influence key pathophysiological processes that underpin asthma may identify new, more effective asthma therapies, particularly for females with severe, poorly controlled asthma.</div><div>We assessed the effects of oral ethinylestradiol/levonorgestrel (representing OCP use) and depot-medroxyprogesterone acetate (DMPA) and estradiol injections on key features of experimental asthma, and determined their effects on glucose transporter-1 (GLUT-1). The effects of OCP use on clinical asthma outcomes, and the relationships between estrogen receptors and type 2 (T2), non-T2, and GLUT-1 responses, in clinical asthma were also determined.</div><div>OCP and DMPA reduce T2 responses, disease features, and lung expression of GLUT-1, whereas estradiol increases lung expression of GLUT-1, and results in severe, corticosteroid-insensitive, neutrophil-enriched disease, in experimental asthma. OCP use is associated with reduced T2 cytokine and GLUT-1 responses in clinical asthma. GLUT-1 expression is increased in sputum of severe asthmatics, and positively correlates with estrogen receptor expression and both T2 and non-T2 inflammatory responses. Significantly, OCP or GLUT-1 inhibition protects against obesity-associated or estradiol-induced, severe, experimental asthma, respectively.</div><div>Together, these data show how female sex hormones and the OCP likely modulate asthma severity by modifying GLUT-1 responses in the airways.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 656-667"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531659","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":"Antibiotic-induced dysbiosis of the ocular microbiome affects corneal circadian rhythmic activity in mice","authors":"Xinwei Jiao ,&nbsp;Yan Li ,&nbsp;Yu Hu ,&nbsp;Ruyu Yan ,&nbsp;Ting Fu ,&nbsp;Jun Liu ,&nbsp;Zhijie Li","doi":"10.1016/j.mucimm.2025.01.010","DOIUrl":"10.1016/j.mucimm.2025.01.010","url":null,"abstract":"<div><div>The ocular surface microbiota plays a critical role in maintaining corneal homeostasis, but its disruption and subsequent effects on corneal functions remain poorly understood. This study investigates how antibiotic-induced microbial depletion affects the corneal circadian transcriptome in C57BL/6J mice. Dysbiosis was induced using a topical antibiotic cocktail, and RNA sequencing was employed to analyze gene expression across eight time points over 24 h. Antibiotic treatment disrupted corneal circadian rhythms, eliminating rhythmicity in 1,812 genes and introducing rhythmicity in 1,928 previously arrhythmic genes. Furthermore, epithelial adhesion was impaired, inflammation was elevated, and neural sensitivity was reduced. More than 50 % of ocular microbial genera exhibited daily oscillations, with six genera showing significant correlations with corneal rhythmic transcripts. Additionally, the administration of TLR agonists restored circadian gene expression patterns, with partial recovery of corneal barrier function and immune homeostasis, further highlighting the potential of microbiota-targeted therapies in treating ocular surface disorders. These findings underscore the critical role of the ocular microbiota in regulating corneal health and suggest that restoring microbial balance via TLR activation may offer new therapeutic avenues for eye diseases.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 562-582"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374452","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":"Airway epithelial cells as drivers of severe asthma pathogenesis","authors":"Del Dorscheid ,&nbsp;Gail M. Gauvreau ,&nbsp;Steve N. Georas ,&nbsp;Pieter S. Hiemstra ,&nbsp;Gilda Varricchi ,&nbsp;Bart N. Lambrecht ,&nbsp;Gianni Marone","doi":"10.1016/j.mucimm.2025.03.003","DOIUrl":"10.1016/j.mucimm.2025.03.003","url":null,"abstract":"<div><div>Our understanding of the airway epithelium’s role in driving asthma pathogenesis has evolved over time. From being regarded primarily as a physical barrier that could be damaged <em>via</em> inflammation, the epithelium is now known to actively contribute to asthma development through interactions with the immune system. The airway epithelium contains multiple cell types with specialized functions spanning barrier action, mucociliary clearance, immune cell recruitment, and maintenance of tissue homeostasis. Environmental insults may cause direct or indirect injury to the epithelium leading to impaired barrier function, epithelial remodelling, and increased release of inflammatory mediators. In severe asthma, the epithelial barrier repair process is inhibited and the response to insults is exaggerated, driving downstream inflammation. Genetic and epigenetic mechanisms also maintain dysregulation of the epithelial barrier, adding to disease chronicity. Here, we review the role of the airway epithelium in severe asthma and how targeting the epithelium can contribute to asthma treatment.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 524-536"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742558","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":"Tear duct M cells exacerbate allergic conjunctivitis by facilitating germinal-center reactions","authors":"Yuki Oya ,&nbsp;Shunsuke Kimura ,&nbsp;Maho Uemura ,&nbsp;Yumiko Fujimura ,&nbsp;Koji Hase","doi":"10.1016/j.mucimm.2025.01.009","DOIUrl":"10.1016/j.mucimm.2025.01.009","url":null,"abstract":"<div><div>The ocular mucosal surface regularly encounters external materials in the air and tear fluids. Microfold (M) cells, specialized epithelial cells for antigen uptake, are present in tear duct-associated lymphoid tissue (TALT) within the nasolacrimal sac; however, their immunological significance is unclear. We generated <em>Krt5</em>-Cre <em>Tnfrsf11a</em>^flox/flox mice, which lack functional M cells in the TALT, as evidenced by the absence of M-cell markers and reduced nanoparticle uptake. M cell deficiency resulted in fewer T follicular helper (Tfh) and germinal center (GC) B cells in the TALT under steady-state conditions. Upon induction of allergic conjunctivitis, control mice exhibited itching and increased Tfh and immunoglobulin E (IgE⁺) GC B cells in the TALT. However, M cell-deficient mice showed ameliorated allergic symptoms with fewer Tfh and IgE⁺ GC B cells. These findings suggest that M cells in TALT contribute to ocular surface immunosurveillance, whereas, upon allergen exposure, they play a critical role in the development of allergic conjunctivitis.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 549-561"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122946","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":"Spatially separated epithelium-associated and lamina propria neutrophils present distinct functional identities in the inflamed colon mucosa","authors":"Lenore K. Yalom ,&nbsp;Caroline J. Herrnreiter ,&nbsp;Triet M. Bui ,&nbsp;Joey Lockhart ,&nbsp;Enzo B. Piccolo ,&nbsp;Xingsheng Ren ,&nbsp;Cenfu Wei ,&nbsp;Anastasiia Serdiukova ,&nbsp;Edward B. Thorp ,&nbsp;Parambir S. Dulai ,&nbsp;Ronen Sumagin","doi":"10.1016/j.mucimm.2025.02.008","DOIUrl":"10.1016/j.mucimm.2025.02.008","url":null,"abstract":"<div><div>Inflammatory Bowel Disease (IBD) features <em>en masse</em> neutrophil (PMN) infiltration of the colon tissue, where PMNs occupy spatially distinct niches, including the lamina propria mucosa (LPNs) and the crypt epithelium (epithelium-associated neutrophils or EANs). Spatial PMN localization is currently used as a clinical disease scoring parameter, and EAN presence has been correlated with disease severity prognosis and reduced response to therapy. Surprisingly, although PMN heterogeneity and their clinical relevance in IBD is now well-recognized, localization-driven PMN specialization has not been investigated. We found that following initial PMN influx during the active disease phase, EANs were near-completely resolved in both UC remission patients and in murine colitis, whereas LPNs persisted throughout the resolution phase, implicating EANs as likely drivers of disease. Local profiling of transcriptional programs (by murine and human single-cell RNA sequencing, coupled with human spatial RNA transcriptomics) and functional phenotypes, including real-time intravital imaging of murine LPNs versus EANs in inflamed colon revealed LPNs and EANs to have distinct functional identities. LPN programs allowed for heightened motility and pathogen uptake, whereas EANs were overrepresented by hyperactivated/pro-apoptotic states with elevated ROS and inflammatory TNFα production. Thus, we demonstrate that colon LPNs and EANs have distinct functional identities, with EANs exhibiting activated states and apparent cytotoxicity, which may actively contribute to tissue damage. Our findings further identify EANs as potential therapeutic targets for improving mucosal healing and sustaining clinical remission in UC.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 685-699"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586255","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}