Mucosal Immunology最新文献_第6页

Systemic IgE promotes allergic rhinitis by licensing Th2-to-Tfh conversion and local IgE production 全身性IgE通过允许th2到tfh的转化和局部IgE的产生促进变应性鼻炎。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-05-23 DOI: 10.1016/j.mucimm.2026.100351

Takuya Nakai, Saya Tezuka, Takumi Adachi, Tatsuo Ueda, Ayumi Fukuoka, Masakiyo Nakahira, Koubun Yasuda, Shiori Egashira, Yu-Chen Liu, Daisuke Okuzaki, Etsushi Kuroda, Kazufumi Matsushita

{"title":"Systemic IgE promotes allergic rhinitis by licensing Th2-to-Tfh conversion and local IgE production","authors":"Takuya Nakai, Saya Tezuka, Takumi Adachi, Tatsuo Ueda, Ayumi Fukuoka, Masakiyo Nakahira, Koubun Yasuda, Shiori Egashira, Yu-Chen Liu, Daisuke Okuzaki, Etsushi Kuroda, Kazufumi Matsushita","doi":"10.1016/j.mucimm.2026.100351","DOIUrl":"10.1016/j.mucimm.2026.100351","url":null,"abstract":"<div><div>Although systemic allergen-specific IgE is an essential biomarker for allergic rhinitis (AR), its mechanistic contribution to symptom development remains unclear. Here, using mouse models, we investigated how systemic antigen-specific IgE influences AR symptoms and local type 2 inflammation. Mice were adoptively sensitized with ovalbumin (OVA)-specific IgE (OVA-IgE) and/or <em>in vitro</em>–differentiated OVA-specific Th2 (OVA-Th2) cells, followed by repeated intranasal OVA exposure. AR symptoms (sneezing) and the appearance of IgE-producing cells in the cervical lymph nodes (cLNs) and nasopharynx-associated lymphoid tissue were observed only in mice that received both OVA-Th2 cells and OVA-IgE. These responses were absent in recipients lacking factors required for IgE production, <em>Rag2</em><sup>−/−</sup>, <em>Aid</em><sup>−/−</sup>, and <em>Stat6</em><sup>−/−</sup> mice, or in mice receiving OVA-Th2 cells deficient in IL-4–producing T follicular helper (Tfh) cell differentiation. Notably, when IgE-independent mast cell activation was induced by repeated intranasal administration of compound 48/80 in mice that had received OVA-Th2 cells, subsequent OVA challenge elicited OVA-specific AR symptoms and induced IgE-producing cells in the cLNs. Single-cell RNA sequencing revealed that systemic OVA-IgE facilitated the differentiation of OVA-Th2 cells into Tfh cells upon OVA challenge. Together, systemic IgE-mediated mast cell/basophil activation promoted Th2-to-Tfh differentiation and local IgE production, thereby contributing to the AR symptoms.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100351"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Learning immunology from mothers and babies 向母亲和婴儿学习免疫学。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-05-30 DOI: 10.1016/j.mucimm.2026.100353

Lucien H. Turner, Jiahui Sun, Alexander E. Brady, Ujjwal Adhikari, Ngan N.M. Nguyen, Miguel A.B. Mercado, Satomi Ando, Raymond E. Diep, Giang Pham, Meghana Madabhushi, David B. Haslam, Koichi Araki, Sing Sing Way

{"title":"Learning immunology from mothers and babies","authors":"Lucien H. Turner, Jiahui Sun, Alexander E. Brady, Ujjwal Adhikari, Ngan N.M. Nguyen, Miguel A.B. Mercado, Satomi Ando, Raymond E. Diep, Giang Pham, Meghana Madabhushi, David B. Haslam, Koichi Araki, Sing Sing Way","doi":"10.1016/j.mucimm.2026.100353","DOIUrl":"10.1016/j.mucimm.2026.100353","url":null,"abstract":"<div><div>Pregnancy is an immunological marvel allowing intimate approximation between genetically discordant tissues of maternal and fetal origin. Shared immunity across the maternal-fetal dyad including intact cells of maternal and fetal origin establishing microchimerism in both individuals after parturition and protection by vertically transferred maternal IgG antibodies are increasingly recognized. Nonetheless, basic questions regarding why mothers do not reject allogeneic fetal tissues and why developing fetal immune cells do not reject allogenic maternal tissue remain unresolved. Establishing how this essential process works holds exciting promise for new therapeutic strategies for common disorders linked with fetal intolerance such as stillbirth, preeclampsia and preterm birth. Besides translational application for improving the health of children through improved pregnancy outcomes, pregnancy also represents an incredibly instructive platform for investigating how immunology works, which can be applied to other physiological contexts where expanded immune tolerance is desired. This perspective highlights several emerging immunological considerations from a pregnancy-focused viewpoint, including maternal immune cell memory, microchimerism and vertically transferred protective antibodies, with particular attention to unresolved questions and application to immunity in non-reproductive contexts.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100353"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ADP-ribosylation factor 1 sustains regulatory T cell function and mucosal immune homeostasis in ulcerative colitis adp核糖基化因子1在溃疡性结肠炎中维持调节性T细胞功能和粘膜免疫稳态。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-06-25 DOI: 10.1016/j.mucimm.2026.100368

Hua-Hua Liu, Shu-Pei Wang, Shuang-Shuang Liu, Yue-Tong Wang, Xiang-Guo Shen, Ji-Min Zhu, Xi-Zhong Shen, Li-Hao Huang, Tao-Tao Liu

{"title":"ADP-ribosylation factor 1 sustains regulatory T cell function and mucosal immune homeostasis in ulcerative colitis","authors":"Hua-Hua Liu, Shu-Pei Wang, Shuang-Shuang Liu, Yue-Tong Wang, Xiang-Guo Shen, Ji-Min Zhu, Xi-Zhong Shen, Li-Hao Huang, Tao-Tao Liu","doi":"10.1016/j.mucimm.2026.100368","DOIUrl":"10.1016/j.mucimm.2026.100368","url":null,"abstract":"<div><div>Dysregulation of regulatory T cells (Tregs) is a hallmark of immune imbalance in ulcerative colitis (UC), in which their suppressive function relies heavily on post-translational modifications and the stabilization of the transcription factor Foxp3. However, the upstream regulatory mechanisms remain poorly understood. Here, we identify ADP-ribosylation factor 1 (<em>Arf1</em>) as a key regulator of Treg function. Clinical samples from UC patients revealed an inverse correlation between <em>ARF1</em> expression in Tregs and disease severity. Using a Treg-specific <em>Arf1</em> knockout mouse model, we demonstrate that <em>Arf1</em> deficiency impairs induced Treg (iTreg) differentiation, disrupts suppressive function, and aggravates T cell transfer-induced colitis. Mechanistically, <em>Arf1</em> sustains mitochondrial integrity and represses histone deacetylase 9 (<em>Hdac9</em>), thereby enhancing FOXP3 acetylation and protein stability. These findings establish <em>Arf1</em> as a critical upstream modulator of Treg cell function and intestinal immune homeostasis, and highlight the ARF1–HDAC9–FOXP3 axis as a promising target for Treg-based therapeutic strategies in UC.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100368"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148331274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Postbiotic Lactobacillus sakei CVL-001 promotes mucosal tolerance via NOD2-dependent programming of tolerogenic CD11c+ antigen-presenting cells 生后的堺乳酸菌CVL-001通过nod2依赖性编程的耐受性CD11c+抗原呈递细胞促进粘膜耐受。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-06-27 DOI: 10.1016/j.mucimm.2026.100371

Dong-Yeon Kim, Tae-Sung Lee, Do-Hyeon Jung, Yeong-Jun Kim, Yun-Ji Lee, In-Su Seo, Wan-Gyu Kim, Jung Joo Hong, Jong-Hwan Park

{"title":"Postbiotic Lactobacillus sakei CVL-001 promotes mucosal tolerance via NOD2-dependent programming of tolerogenic CD11c+ antigen-presenting cells","authors":"Dong-Yeon Kim, Tae-Sung Lee, Do-Hyeon Jung, Yeong-Jun Kim, Yun-Ji Lee, In-Su Seo, Wan-Gyu Kim, Jung Joo Hong, Jong-Hwan Park","doi":"10.1016/j.mucimm.2026.100371","DOIUrl":"10.1016/j.mucimm.2026.100371","url":null,"abstract":"<div><div>Postbiotics offer improved safety and stability over live probiotics for modulating intestinal immunity, yet the receptor-mediated mechanisms underlying mucosal tolerance remain unclear. Nucleotide-binding oligomerization domain 2 (NOD2), a cytosolic sensor of bacterial cell wall components and a major genetic risk factor for inflammatory bowel disease (IBD), may link microbial signals to regulatory immune programs. Here, we show that heat-killed <em>Lactobacillus sakei</em> CVL-001 (HK CVL-001) promotes intestinal homeostasis through NOD2 signaling. HK CVL-001, but not its culture supernatant, significantly alleviated dextran sulfate sodium (DSS)-induced colitis, whereas this protection was completely lost in NOD2<sup>−/−</sup> mice. Treatment suppressed pro-inflammatory cytokines (IL-6, IL-1β), increased IL-10, and expanded Foxp3<sup>+</sup> regulatory T cells (Tregs) and CD103<sup>+</sup> tolerogenic antigen-presenting cell (APC) populations. In vitro, HK CVL-001 directly induced CD103 expression in BMDCs in a NOD2-dependent manner, enhancing their capacity to drive Treg differentiation. This effect was accompanied by upregulation of <em>Irf8</em> and <em>Irf4</em>, along with expansion of both CD11b<sup>−</sup> and CD11b<sup>+</sup> CD103<sup>+</sup> APC populations. A functional role for NOD2 signaling within CD11c<sup>+</sup> APCs was confirmed using CD11c-Cre × NOD2<sup>fl/fl</sup> mice and adoptive transfer experiments. These findings support a NOD2-dependent CD11c<sup>+</sup> APC–Treg regulatory axis underlying postbiotic-induced mucosal tolerance.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100371"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex-specific in utero reprogramming of lung immunity 子宫内肺免疫的性别特异性重编程。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-06-01 DOI: 10.1016/j.mucimm.2026.100352

Anthony Maxwell, Audrey Couturier, Annie Thy Nguyen, Savannah Schick, Aditi Singh, Elizabeth Findeis, Jayanth Ramadoss, Judy Westrick, Nicholas Peraino, Paul M. Stemmer, Albert M. Levin, Gil Mor, Jiahui Ding

{"title":"Sex-specific in utero reprogramming of lung immunity","authors":"Anthony Maxwell, Audrey Couturier, Annie Thy Nguyen, Savannah Schick, Aditi Singh, Elizabeth Findeis, Jayanth Ramadoss, Judy Westrick, Nicholas Peraino, Paul M. Stemmer, Albert M. Levin, Gil Mor, Jiahui Ding","doi":"10.1016/j.mucimm.2026.100352","DOIUrl":"10.1016/j.mucimm.2026.100352","url":null,"abstract":"<div><div>Lung mucosal immunity must balance effective antimicrobial defense with tightly controlled inflammatory responses to maintain pulmonary homeostasis. Although sex differences in respiratory disease susceptibility are well documented, the developmental origins of these differences and their modulation by prenatal environmental exposures remain poorly defined. Here, we tested the hypothesis that prenatal benzene exposure establishes sex-specific reprogramming of lung mucosal immunity during fetal development. Using a controlled inhalation exposure model in pregnant C57BL/6 mice, we characterized immune responses in fetal and postnatal lungs under baseline conditions and following viral challenge. We found that female offspring displayed heightened type I interferon signaling and enhanced viral clearance, accompanied by exaggerated inflammatory pathology and altered expressions of DREAM and A20. In contrast, male offspring exhibited augmented proinflammatory cytokine production following lipopolysaccharide challenge. Alveolar macrophages from prenatally benzene exposed offspring demonstrated persistent inflammatory priming, indicating durable alteration of innate immune populations. These findings demonstrate that lung mucosal immune development is intrinsically sex-dependent and that prenatal environmental pollutants interact with fetal sex to durably reprogram respiratory immunity. Together, our results identify in utero environmental exposure as a critical determinant of sex-specific mucosal immune trajectories that shape postnatal responses to infection.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100352"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pregnancy stages differentially impact maternal alveolar macrophages' function and immunity to SARS-CoV-2 infection 妊娠阶段差异影响母体肺泡巨噬细胞功能和对SARS-CoV-2感染的免疫。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-06-24 DOI: 10.1016/j.mucimm.2026.100366

Alina Fokina, Lisabeth Pimenov-Reifeltshammer, Anastasiya Hladik, Karin Lakovits, Asma Farhat, Florian Deckert, Mariem Radhouani, Jessica Broesamlen, Fanzhe Meng, Riem Gawish, Sylvia Knapp

{"title":"Pregnancy stages differentially impact maternal alveolar macrophages' function and immunity to SARS-CoV-2 infection","authors":"Alina Fokina, Lisabeth Pimenov-Reifeltshammer, Anastasiya Hladik, Karin Lakovits, Asma Farhat, Florian Deckert, Mariem Radhouani, Jessica Broesamlen, Fanzhe Meng, Riem Gawish, Sylvia Knapp","doi":"10.1016/j.mucimm.2026.100366","DOIUrl":"10.1016/j.mucimm.2026.100366","url":null,"abstract":"<div><div>Pregnancy comes with complex immune adaptations to support the specific needs of each pregnancy stage. Infections during pregnancy pose an additional challenge in keeping the fine balance between protective and detrimental immune activation. Whether mucosal immunity adapts to different pregnancy stages is poorly understood. Through detailed profiling of lung immune cells, we discovered a selective expansion of tissue-resident alveolar macrophages (TR-AMs) during late gestation. Using scRNA-seq we identified TR-AMs as the functionally most altered pulmonary immune cells that exhibited an anti-inflammatory transcriptional state, reduced cellular interactions and diminished responsiveness to viral ligands. This gestation-stage-specific adaptation shaped the response to SARS-CoV-2 infection. While early-stage pregnant animals showed an enhanced anti-viral response and accelerated viral clearance, late-stage pregnancy infection mirrored the dampened immune state of TR-AMs and prevented exaggerated lung tissue damage. We postulate that pulmonary immune adaptations in pregnancy augment defenses to protect fetal development in early stages, yet preserve maternal fitness required for parturition at later stages.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100366"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GPR15-GPR15L axis controls colon natural TCRαβ cells residency and enteroendocrine cell homeostasis to calibrate metabolism GPR15-GPR15L轴控制结肠非常规TCRαβ细胞驻留和肠内分泌细胞稳态，校准代谢。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-06-25 DOI: 10.1016/j.mucimm.2026.100370

Borja Ocón, Nanna C. Giercksky Nilssen, Belén Rivero-Gutiérrez, Nicole H. Lazarus, Yuhan Bi, Junliang Pan, Eugene C. Butcher

{"title":"GPR15-GPR15L axis controls colon natural TCRαβ cells residency and enteroendocrine cell homeostasis to calibrate metabolism","authors":"Borja Ocón, Nanna C. Giercksky Nilssen, Belén Rivero-Gutiérrez, Nicole H. Lazarus, Yuhan Bi, Junliang Pan, Eugene C. Butcher","doi":"10.1016/j.mucimm.2026.100370","DOIUrl":"10.1016/j.mucimm.2026.100370","url":null,"abstract":"<div><div>GPR15 is a colon homing receptor, but its pattern of expression among gut intestinal intraepithelial lymphocytes and its role on intestinal intraepithelial lymphocyte (IEL) and epithelial homeostasis, as well as systemic metabolism and hormones remain unknown. GPR15L is the only ligand for GPR15 described to date, but whether this is the only functional ligand for GPR15 has not been formally explored.</div><div>Here we show that GPR15 is expressed by mouse colon IELs, namely natural TCRαβ CD8αα+/− cells. These are reduced in the <em>Gpr15</em>−/− and <em>Gpr15L</em>−/− mice colon intraepithelial compartment. This translates into an overrepresentation of enteroendocrine cells in the colonic epithelium, elevated plasma serotonin and increased insulin secretion in response to local glucose administration. Competitive bone marrow chimeric mice confirm that GPR15L is the only functional colon-expressed chemokine ligand for GPR15. Human GPR15 is expressed and functional, recognizes mouse GPR15L and rescues the phenotypes associated with GPR15 deficiency in our novel GPR15 humanized model, which recapitulates features of the human colon immunobiology more closely than wild type mice.</div><div>This work extends to the colon and TCRαβ CD8αα T cells the complex natural gut-resident T cell vs intestinal enteroendocrine cells crosstalk that controls systemic hormones and metabolism.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100370"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148331291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioinformatics roadmap for characterizing the gut microbiome to study its interactions and associations with the gut mucosal immune system 表征肠道微生物组的生物信息学路线图，以研究其与肠道黏膜免疫系统的相互作用和关联。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-07-02 DOI: 10.1016/j.mucimm.2026.100375

Muhammad Zohaib Anwar, Miguel Dario Prieto, William W.L. Hsiao

{"title":"Bioinformatics roadmap for characterizing the gut microbiome to study its interactions and associations with the gut mucosal immune system","authors":"Muhammad Zohaib Anwar, Miguel Dario Prieto, William W.L. Hsiao","doi":"10.1016/j.mucimm.2026.100375","DOIUrl":"10.1016/j.mucimm.2026.100375","url":null,"abstract":"<div><div>Cataloging the gut microbiome and understanding its interactions and association with the host immune system remains relevant to identify potential treatments for complex chronic diseases, including cancer. Studying the gut microbiome is more accessible than ever, thanks to the dramatic cost reduction of sequencing and the continuous improvements in bioinformatics and machine learning approaches. A plethora of bioinformatics and statistical methods are currently available to analyze gut microbiome sequencing data and evaluate its interactions with the host immune system across health and disease. This review summarizes different approaches and selected bioinformatics tools for gut microbiome data analysis. Furthermore, we underline methods for integrating and correlating sequencing data with other biological datasets, such as those resulting from metabolomics and immunological assays. Overall, this review provides a roadmap to help researchers with limited programming experience understand the approaches available to study the gut microbial community in relation to their topic of interest.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100375"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Candidalysin promotes fungal-specific Th17 CD4 T cell differentiation and protective systemic immunogenicity 念珠菌素促进真菌特异性Th17 CD4 T细胞分化和保护性全身免疫原性。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-05-07 DOI: 10.1016/j.mucimm.2026.100348

Ngan N.M. Nguyen, Alexander E. Brady, David B. Haslam, Corey Frazer, Giang Pham, Richard J. Bennett, Sing Sing Way

{"title":"Candidalysin promotes fungal-specific Th17 CD4 T cell differentiation and protective systemic immunogenicity","authors":"Ngan N.M. Nguyen, Alexander E. Brady, David B. Haslam, Corey Frazer, Giang Pham, Richard J. Bennett, Sing Sing Way","doi":"10.1016/j.mucimm.2026.100348","DOIUrl":"10.1016/j.mucimm.2026.100348","url":null,"abstract":"<div><div>Commensal microbes can cause invasive infection but can also stimulate protective immune responses as exemplified by the gut pathobiont <em>Candida albicans.</em> This species primes systemic Th17 immunogenicity which protects against disseminated infection, and yet the fungal determinants driving protection remain uncertain. Here we show an essential role for the cytolytic toxin candidalysin for <em>C. albicans</em> colonization-induced systemic Th17 immunogenicity and protection against invasive infection. Mice intestinally colonized with candidalysin-deficient cells show reduced accumulation of CD4 T cells with defined fungal specificity, despite similar intestinal colonization levels to wildtype <em>C. albicans</em> cells. Fungal-specific RORγt+ CD4 T cells are particularly reduced together with their production of IL17A and IL17F cytokines, whereas expression of transcription factors and production of cytokines representative of other helper T cell lineages are unaffected. Protection against fungemia conferred by colonization with wildtype <em>C. albicans</em> is overturned in mice colonized with candidalysin-deficient cells as shown by increased fungal pathogen burden and reduced survival after intravenous infection. These results establish the necessity for candidalysin for priming Th17 fungal-specific adaptive immune cells and highlight paradoxical protective roles for this fungal virulence factor for promoting host defense against invasive systemic disease.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100348"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13255055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fibrinogen and lipopolysaccharide promote TLR4-dependent glucocorticoid resistance in airway mycosis-driven allergic airway disease 纤维蛋白原和脂多糖促进tlr4依赖性糖皮质激素抵抗气道真菌驱动的过敏性气道疾病。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-06-01 DOI: 10.1016/j.mucimm.2026.100354

Y. Zeng, X. Huang, G. Liang, K. Tang, K.E. Mauk, H. Sun, Y. Zhang, Z. Zeng, L. Song, K. Polsky, Y. Wu, C.T. Landers, E.Z. Otukoya, L.H. Bimler, F. Kheradmand, A.U. Luong, Y. Guo, J.M. Knight, D.B. Corry

{"title":"Fibrinogen and lipopolysaccharide promote TLR4-dependent glucocorticoid resistance in airway mycosis-driven allergic airway disease","authors":"Y. Zeng, X. Huang, G. Liang, K. Tang, K.E. Mauk, H. Sun, Y. Zhang, Z. Zeng, L. Song, K. Polsky, Y. Wu, C.T. Landers, E.Z. Otukoya, L.H. Bimler, F. Kheradmand, A.U. Luong, Y. Guo, J.M. Knight, D.B. Corry","doi":"10.1016/j.mucimm.2026.100354","DOIUrl":"10.1016/j.mucimm.2026.100354","url":null,"abstract":"<div><div>Glucocorticoid-refractory asthma is a severe disease type linked to both T helper type 2 (T2) high and T2 low, neutrophil-high asthma endotypes, but the mechanisms governing glucocorticoid resistance are largely unknown. We show that glucocorticoid-resistant mouse allergic airway disease is linked to airway mycosis and lung-specific production of fibrinogen cleavage products (cryptokines). Mice challenged with the allergenic fungus <em>Aspergillus niger</em> and low-dose inhaled lipopolysaccharide (LPS) showed exaggerated airway hyperresponsiveness (AHR), developed T2 high and neutrophilic airway inflammation recapitulating severe asthma. AHR was not attenuated by glucocorticoid therapy, but required expression of Toll-like receptor 4 (TLR4). Low-dose intranasal LPS alone induced AHR in a manner previously shown for <em>Aspergillus</em> proteinase-derived cryptokines that required TLR4. We show further that cryptokines significantly enhance fibrinogen production in both the mouse lung and from primary human airway epithelial cells and that cryptokine-induced AHR is glucocorticoid resistant. Thus, glucocorticoid resistance in asthma may in part result from airway-specific production of the TLR4 ligands cryptokines and LPS. These findings suggest novel approaches to the management of glucocorticoid-resistant asthma.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100354"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0