Mucosal Immunology最新文献_第2页

Type-I interferons in Vulvovaginal Candidiasis: Mechanism of epithelial early defense and immune regulation against Candida albicans i型干扰素在外阴阴道念珠菌病中的作用：上皮早期防御机制和对白色念珠菌的免疫调节。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-10-01 DOI: 10.1016/j.mucimm.2025.07.001

Emilse Rodriguez , Constanza Savid-Frontera , Sofía C. Angiolini , María Luisa Hernáez-Sánchez , María Soledad Miró , María Estefania Viano , Paula A. Icely , Cinthia C. Stempin , María Cecilia Rodriguez-Galan , Concha Gil , Claudia E. Sotomayor

{"title":"Type-I interferons in Vulvovaginal Candidiasis: Mechanism of epithelial early defense and immune regulation against Candida albicans","authors":"Emilse Rodriguez , Constanza Savid-Frontera , Sofía C. Angiolini , María Luisa Hernáez-Sánchez , María Soledad Miró , María Estefania Viano , Paula A. Icely , Cinthia C. Stempin , María Cecilia Rodriguez-Galan , Concha Gil , Claudia E. Sotomayor","doi":"10.1016/j.mucimm.2025.07.001","DOIUrl":"10.1016/j.mucimm.2025.07.001","url":null,"abstract":"<div><div>Vulvovaginal candidiasis (VVC) is a mucosal infection predominantly caused by <em>Candida albicans</em>, affecting over three-quarters of immunocompetent women worldwide. While the female genital tract mucosa is the primary defense against the fungus, the specific immune mechanisms involved in this host-pathogen interaction remain largely unknown. In this study, we explored the relevance of type-I interferons (IFNs-I) pathway using both <em>in vitro</em> and <em>in vivo</em> models of VVC. Our quantitative proteomic analysis revealed that <em>C. albicans</em> induces the activation of the IFNs-I pathway in human epithelial cells (ECs) of the female genital tract shortly after exposure to the fungus. Additionally, we identified β-glucans as a crucial fungal component involved in triggering this pathway. Using a VVC model in IFN-α/β receptor-deficient <em>(Ifnar1-/-)</em> mice, we demonstrated that IFNs-I regulate the fungal burden, <em>C. albicans</em> epithelial invasion, polymorphonuclear neutrophils (PMNs) recruitment, inflammatory tissue response, local cytokine balance, and the composition of T cell subsets in the draining lymph nodes. These findings underscore the pivotal role of the IFNs-I pathway in ECs-mediated responses against <em>C. albicans</em>, especially in the early stages of VVC development, offering insights into potential therapeutic targets for this condition.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 5","pages":"Pages 1124-1138"},"PeriodicalIF":7.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619091","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}

引用次数: 0

Microbiota promote enhanced CD39 expression in γδ intraepithelial lymphocytes through the activation of TCR and IL-15 signaling 微生物群通过激活TCR和IL-15信号通路促进CD39在γδ上皮内淋巴细胞中的表达。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-10-01 DOI: 10.1016/j.mucimm.2025.07.005

Sara Alonso , Harsimran Kaur , Luo Jia , Mai-Uyen Nguyen , Alyssa Laguerta , Andrew Fong , Neema Skariah , Rafael J. Argüello , Michael P. Verzi , Mahima Swamy , Ken S. Lau , Karen L. Edelblum

{"title":"Microbiota promote enhanced CD39 expression in γδ intraepithelial lymphocytes through the activation of TCR and IL-15 signaling","authors":"Sara Alonso , Harsimran Kaur , Luo Jia , Mai-Uyen Nguyen , Alyssa Laguerta , Andrew Fong , Neema Skariah , Rafael J. Argüello , Michael P. Verzi , Mahima Swamy , Ken S. Lau , Karen L. Edelblum","doi":"10.1016/j.mucimm.2025.07.005","DOIUrl":"10.1016/j.mucimm.2025.07.005","url":null,"abstract":"<div><div>Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IEL) provide continuous surveillance of the intestinal epithelium. We report that mice harboring a microbiota-specific hyperproliferative γδ IEL (γδ<sup>HYP</sup>) phenotype also upregulate the expression of the ectonucleotidase CD39, a marker of regulatory γδ T cells. Enhanced TCR and IL-15 signaling correlates with a progression from a naïve-like CD39<sup>neg</sup> γδ IEL to a more mature, tissue-adapted CD39<sup>hi</sup> IEL population. We found that TCRγδ activation drives CD122-mediated CD39 upregulation on γδ<sup>HYP</sup> IELs and increased mucosal IL-15 further amplifies CD39 expression in these cells. Further investigation revealed that CD39 induction requires sustained exposure to the γδ<sup>HYP</sup>-associated microbiota. Moreover, CD39<sup>hi</sup> γδ IELs exhibit a reduced capacity to produce pro-inflammatory cytokine, which may explain the lack of histopathology in γδ<sup>HYP</sup> mice. Overall, our study identifies a previously unappreciated mechanism by which an altered microbiota amplifies CD39 expression on γδ<sup>HYP</sup> IELs, leading to the expansion of γδ IELs with regulatory potential.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 5","pages":"Pages 1184-1198"},"PeriodicalIF":7.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668044","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}

引用次数: 0

M2 macrophage-derived Apolipoprotein E promotes fibroblast MMPs expression via LRP1-ERK signaling in chronic rhinosinusitis with nasal polyps M2巨噬细胞来源的载脂蛋白E通过LRP1-ERK信号通路促进慢性鼻窦炎伴鼻息肉成纤维细胞MMPs的表达。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-10-01 DOI: 10.1016/j.mucimm.2025.07.004

Ying Zhu , Jiayao Zhou , Ru Tang , Shiyao Zhang , Chunyu Luo , Yuelong Gu , Shilei Pu , Song Mao , Hai Lin , Haibo Ye , Zhipeng Li , Weitian Zhang

{"title":"M2 macrophage-derived Apolipoprotein E promotes fibroblast MMPs expression via LRP1-ERK signaling in chronic rhinosinusitis with nasal polyps","authors":"Ying Zhu , Jiayao Zhou , Ru Tang , Shiyao Zhang , Chunyu Luo , Yuelong Gu , Shilei Pu , Song Mao , Hai Lin , Haibo Ye , Zhipeng Li , Weitian Zhang","doi":"10.1016/j.mucimm.2025.07.004","DOIUrl":"10.1016/j.mucimm.2025.07.004","url":null,"abstract":"<div><div>Apolipoprotein E (APOE) expressed by macrophages modulates allergic inflammation and remodeling of the lower airway. However, its expression and functions in chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear. We sought to investigate the involvement of macrophage derived APOE in the pathogenesis of CRSwNP. APOE expression was evaluated in single cell RNA sequencing data and then validated in tissues from healthy controls (HCs), chronic rhinosinusitis without nasal polyps (CRSsNP) and CRSwNP patients. We found that APOE expression was elevated in M2 macrophages of both eosinophilic and non-eosinophilic CRSwNP patients. APOE protein was increased in nasal secretions from CRSwNP patients compared to HCs and CRSsNP patients, while no significant differences were found in serum samples. TGF-β induced APOE secretion in both THP-1 and peripheral blood mononuclear cell (PBMC) differentiated macrophages <em>in vitro</em>. Fibroblast LRP1 was predicted as a potential receptor, with expression correlating positively with APOE levels. In primary nasal fibroblasts, APOE induced MMP2 and MMP9 expression through LRP1-dependent ERK activation. CRSwNP murine model was established in wild type and <em>Apoe</em><sup>-/-</sup> mice, which indicated that <em>Apoe</em> deficiency attenuated NP-like lesions formation and the expression of <em>Lrp1</em> and <em>Mmp2</em> in nasal mucosa. Our data demonstrated that APOE expression is increased in macrophages from both eosinophilic and non-eosinophilic CRSwNP and promotes fibroblast MMP2 and MMP9 expression via LRP1-ERK signaling, which may contribute to tissue remodeling in CRSwNP.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 5","pages":"Pages 1171-1183"},"PeriodicalIF":7.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682800","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}

引用次数: 0

Exogenous ephrin-A3 reverses loss of vaginal epithelial barrier protection in progestin-treated mice 外源性ephrin-A3逆转孕激素处理小鼠阴道上皮屏障保护的丧失。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-10-01 DOI: 10.1016/j.mucimm.2025.06.007

Mohan Liu , Rodolfo D. Vicetti Miguel , Kristen Aceves , Thomas L. Cherpes

{"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":"<div><div>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.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 5","pages":"Pages 1072-1081"},"PeriodicalIF":7.6,"publicationDate":"2025-10-01","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}

引用次数: 0

Single-cell RNA profiling identifies immune cell population shifts in diabetes associated mucosal inflammation 单细胞RNA谱鉴定糖尿病相关粘膜炎症中免疫细胞群的变化。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-10-01 DOI: 10.1016/j.mucimm.2025.06.008

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

{"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":"<div><div>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<sup>δ</sup> 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<sup>+</sup> γ<sup>δ+</sup> T-cells and reduced Tregs in diabetic mice, with parallel findings of elevated CD3<sup>+</sup>IL-17A<sup>+</sup> 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<sup>δ</sup> 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, implicate γ<sup>δ</sup> T-cells as a driving factor and point to them as a potential therapeutic target in periodontitis and other diabetic complications.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 5","pages":"Pages 1082-1097"},"PeriodicalIF":7.6,"publicationDate":"2025-10-01","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}

引用次数: 0

Dysbiosis of the gut microbiome may contribute to the pathogenesis of oral lichen planus through Treg dysregulation 肠道菌群失调可能通过Treg失调导致口腔扁平苔藓的发病。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-10-01 DOI: 10.1016/j.mucimm.2025.05.009

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

{"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":"<div><div>Oral lichen planus (OLP) is a chronic inflammatory disorder with autoimmune features and malignant transformation risk, lacking a definitive treatment, with CD4<sup>+</sup> T cells being pivotal in its pathogenesis. Dysbiosis, an imbalance in the microbiome, is linked to various autoimmune and inflammatory diseases, where CD4<sup>+</sup> 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<sup>+</sup> T cells in OLP. We collected stool and saliva samples from OLP patients, conducting 16S rRNA gene analysis and mass spectrometry, and assessed CD4<sup>+</sup> 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<sup>+</sup> 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.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 5","pages":"Pages 1013-1026"},"PeriodicalIF":7.6,"publicationDate":"2025-10-01","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}

引用次数: 0

TRIM33 prevents the exacerbation of allergic asthma by restricting the overactivation of alveolar macrophages TRIM33通过限制肺泡巨噬细胞的过度活化来防止过敏性哮喘的加重。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-10-01 DOI: 10.1016/j.mucimm.2025.07.003

Jiaoyan Lv , Ziyan Su , Tao Wu , Yujie Tian , Xin Liu , Jiachen Liu , Xiaoguang Li , Wenlong Lai , Chen Dong , Li Wu

{"title":"TRIM33 prevents the exacerbation of allergic asthma by restricting the overactivation of alveolar macrophages","authors":"Jiaoyan Lv , Ziyan Su , Tao Wu , Yujie Tian , Xin Liu , Jiachen Liu , Xiaoguang Li , Wenlong Lai , Chen Dong , Li Wu","doi":"10.1016/j.mucimm.2025.07.003","DOIUrl":"10.1016/j.mucimm.2025.07.003","url":null,"abstract":"<div><div>Alveolar macrophages (AMs) and dendritic cells (DCs) are the two major types of primary innate immune cells in allergic asthma and their functions were elaborately regulated during the progression of asthma. Tripartite motif-containing protein 33 (TRIM33) is a multifunctional protein that regulates differentiation and function of immune cells. However, its role in AMs and DCs in the context of allergic asthma remained unclear. Herein, we found that specific deletion of TRIM33 in AM and DCs (<em>Itgax<sup>Cre-GFP</sup>Trim33<sup>fl/fl</sup></em> mice) affected their homeostasis in lung and induced aggravated allergic asthma. Though reduced in number in steady state, antigen-exposed <em>Trim33<sup>−/−</sup></em> CD11b<sup>+</sup> DCs exhibited comparable potency in triggering allergic asthma. Replacing <em>Trim33<sup>−/−</sup></em> AMs with normal AMs could alleviate the aggravated HDM-induced airway inflammation and Th2 responses in <em>Itgax<sup>Cre-GFP</sup>Trim33<sup>fl/fl</sup></em> mice. Moreover, <em>Trim33<sup>−/−</sup></em> AMs exhibited stronger activation status and became an additional cellular source of CCL2 when encountered the allergen, thereby promoting the recruitment of CD11b<sup>+</sup> DCs into lung and draining lymph nodes where they amplifying Th2 responses in <em>Itgax</em><sup>Cre-GFP</sup><em>Trim33</em><sup>fl/fl</sup> mice. Our study revealed a crucial role of TRIM33 in controlling the aggravation of allergic asthma via repressing AM overactivation.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 5","pages":"Pages 1159-1170"},"PeriodicalIF":7.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668045","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}

引用次数: 0

Dynamics of virus-specific CD8+ T cells in the human nasal cavity 病毒特异性CD8+ T细胞在人鼻腔中的动态变化。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-10-01 DOI: 10.1016/j.mucimm.2025.07.007

Joey Ming Er Lim , Sabrina Ottolini , Shou Kit Hang , Martin Daniel Qui , Adeline Chia , Jenny Guek Hong Low , Nina Le Bert , Anthony Tanoto Tan , Antonio Bertoletti

{"title":"Dynamics of virus-specific CD8+ T cells in the human nasal cavity","authors":"Joey Ming Er Lim , Sabrina Ottolini , Shou Kit Hang , Martin Daniel Qui , Adeline Chia , Jenny Guek Hong Low , Nina Le Bert , Anthony Tanoto Tan , Antonio Bertoletti","doi":"10.1016/j.mucimm.2025.07.007","DOIUrl":"10.1016/j.mucimm.2025.07.007","url":null,"abstract":"<div><div>The nasal cavity is the entry site for respiratory viruses. Understanding how the nasal cavity sustains memory CD8+ T cell is essential for improving respiratory virus management and vaccine development. Here, we sampled CD8+ T cells from the upper nasal turbinate and peripheral blood of healthy adults. We analysed their transcriptomic profile and antigen specificity for respiratory (SARS-CoV-2, Influenza A) and non-respiratory (HCMV) viruses.</div><div>Transcriptomic analysis revealed that nasal CD8+ T cells failed to upregulate STAT1 following TCR stimulation, potentially enabling clonal expansion despite the antiproliferative effects of IFN signalling. They also exhibited a cytotoxic, Th1-like profile with tissue-residency markers but lacked TCF7 expression, suggesting limited self-renewal capacity. The CD8+ T cell analysis of antigen specificity demonstrates that local nasal exposure is indispensable for virus-specific CD8+ T cell detection. Only SARS-CoV-2 and influenza-specific but not HCMV-specific CD8+ T cells were detected in the nasal compartment. However, their persistence over time in the nasal cavity appears linked to repetitive viral exposure.</div><div>Our findings provide insights into the adaptations of nasal-resident CD8+ T cells and highlight challenges in eliciting durable nasal T cell immunity, with important implications for vaccine strategies against respiratory pathogens.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 5","pages":"Pages 1218-1227"},"PeriodicalIF":7.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708144","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}

引用次数: 0

Single cell transcriptional analysis of human adenoids identifies molecular features of airway microfold cells 人腺样体单细胞转录分析鉴定气道微褶细胞的分子特征。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-10-01 DOI: 10.1016/j.mucimm.2025.07.006

Samuel Alvarez-Arguedas , Khadijah Mazhar , Andi Wangzhou , Ishwarya Sankaranarayanan , Gabriela Gaona , John T. Lafin , Ron B. Mitchell , Theodore J. Price , Michael U. Shiloh

{"title":"Single cell transcriptional analysis of human adenoids identifies molecular features of airway microfold cells","authors":"Samuel Alvarez-Arguedas , Khadijah Mazhar , Andi Wangzhou , Ishwarya Sankaranarayanan , Gabriela Gaona , John T. Lafin , Ron B. Mitchell , Theodore J. Price , Michael U. Shiloh","doi":"10.1016/j.mucimm.2025.07.006","DOIUrl":"10.1016/j.mucimm.2025.07.006","url":null,"abstract":"<div><div>The nasal, oropharyngeal, and bronchial mucosa are primary contact points for airborne pathogens like <em>Mycobacterium tuberculosis</em> (Mtb), SARS-CoV-2, and influenza virus. While mucosal surfaces can function as both entry points and barriers to infection, mucosa-associated lymphoid tissues (MALT) facilitate early immune responses to mucosal antigens. MALT contains a variety of specialized epithelial cells, including a rare cell type called a microfold cell (M cell) that functions to transport apical antigens to basolateral antigen-presenting cells, a crucial step in the initiation of mucosal immunity. M cells have been extensively characterized in the gastrointestinal (GI) tract in murine and human models. However, the precise development and functions of human airway M cells are unknown. Here, using single-nucleus RNA sequencing (snRNA-seq), we generated an atlas of cells from the human adenoid and identified 26 unique cell types representing basal, club, hillock, and hematopoietic lineages, defined their developmental trajectories, and determined cell-cell relationships. Using trajectory analysis, we found that human airway M cells develop from progenitor club cells and express a gene signature distinct from intestinal M cells. Surprisingly, we also identified a heretofore unknown epithelial cell type demonstrating a robust interferon-stimulated gene signature. Our analysis of human adenoid cells enhances our understanding of mucosal immune responses and the role of M cells in airway immunity. This work also provides a resource for understanding early interactions of pathogens with airway mucosa and a platform for development of mucosal vaccines.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 5","pages":"Pages 1199-1217"},"PeriodicalIF":7.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732357","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}

引用次数: 0

Fibroblast-derived CSF1 maintains colonization of gut mucosal macrophage to resist bacterial infection 成纤维细胞衍生的CSF1维持肠道粘膜巨噬细胞的定植以抵抗细菌感染。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-10-01 DOI: 10.1016/j.mucimm.2025.06.011

Daichi Nonaka , Soichiro Yoshida , Kenta Nakano , Xiaojun Li , Tadashi Okamura , Eiji Umemoto , Taisho Yamada , Miyuki Watanabe , Shozo Jinno , Minako Ito , Makoto Tsuda , Naoto Noguchi , Jean X Jiang , Eriko Sumiya , Shinichiro Sawa

{"title":"Fibroblast-derived CSF1 maintains colonization of gut mucosal macrophage to resist bacterial infection","authors":"Daichi Nonaka , Soichiro Yoshida , Kenta Nakano , Xiaojun Li , Tadashi Okamura , Eiji Umemoto , Taisho Yamada , Miyuki Watanabe , Shozo Jinno , Minako Ito , Makoto Tsuda , Naoto Noguchi , Jean X Jiang , Eriko Sumiya , Shinichiro Sawa","doi":"10.1016/j.mucimm.2025.06.011","DOIUrl":"10.1016/j.mucimm.2025.06.011","url":null,"abstract":"<div><div>Macrophages play essential roles in immune defense and tissue homeostasis, but the mechanisms underlying their colonization in the gut mucosa remain incompletely understood. Here, we identify CSF1, primarily derived from fibroblasts, as the dominant factor maintaining mucosal macrophage colonization, whereas IL-34 deficiency alone has a minimal impact. We reveal that CSF1R ligands originate from distinct cellular sources: macrophages at the upper villus region depend on fibroblast-derived CSF1 and IL-34, while macrophages in the lower villus and the submucosal (lower villus + SM) region are regulated by CSF1 from both fibroblasts and endothelial cells. Additionally, within the lower villus + SM region, CSF1-producing CD81<sup>+</sup> LepR<sup>+</sup> fibroblasts directly interact with CD163<sup>+</sup> macrophages, forming a localized niche. The loss of CSF1 in fibroblasts results in accelerated systemic dissemination of <em>Salmonella</em> Typhimurium, highlighting fibroblast-derived CSF1 as a key regulator of gut macrophage function in host defense. Collectively, our findings uncover a previously unrecognized fibroblast-macrophage crosstalk that governs gut macrophage homeostasis and immunity.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 5","pages":"Pages 1113-1123"},"PeriodicalIF":7.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560556","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}

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