Mucosal Immunology最新文献

{"title":"The neuroendocrine peptide catestatin promotes clearance of cutaneous Staphylococcus aureus through mast cell Mrgpr activation","authors":"Colin Guth,&nbsp;Hannah Dychtenberg,&nbsp;Erin Rudolph,&nbsp;Austin Pozniak,&nbsp;Priyanka Pundir","doi":"10.1016/j.mucimm.2026.03.003","DOIUrl":"10.1016/j.mucimm.2026.03.003","url":null,"abstract":"<div><div>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) is a leading cause of cutaneous infections, underscoring the need for alternative therapeutic strategies. Catestatin (CST), a neuroendocrine antimicrobial peptide produced by neurons and epithelial cells, has been implicated in skin defense against pathogens such as MRSA, though its mechanisms remain unclear. Here, we show that CST expression is upregulated in MRSA-infected skin wounds and that topical CST application significantly accelerates wound healing and reduces MRSA burden in infected murine cutaneous wounds. This effect is dependent on the mast cell-specific G protein-coupled receptor Mrgprb2, the murine ortholog of human MRGPRX2. Notably, CST treatment leads to Mrgprb2-dependent suppression of inflammatory cytokine production and leukocyte infiltration, alongside upregulation of the antimicrobial peptide β-defensin-14. In an immortalized human mast cell line, CST induces MRGPRX2-dependent degranulation, histamine release, prostaglandin D2 production, and cytokine expression. Pharmacological inhibition and western blot analysis reveal that CST activates multiple downstream G protein-dependent signaling pathways in an MRGPRX2-dependent manner. These findings demonstrate that CST promotes wound healing and bacterial clearance by activating mast cells through Mrgprb2, thereby enhancing antimicrobial peptide production. Our study positions CST as a promising mast cell-targeting immunotherapeutic candidate for treating antibiotic-resistant skin infections.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100329"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365537","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":"The Nox2 NADPH oxidase regulates neutrophilic inflammation in the oral cavity","authors":"Shunying Jin ,&nbsp;Richa Singhal ,&nbsp;Jianzhu Luo ,&nbsp;Yasmine H. Higgins ,&nbsp;Kelley N. Cooper ,&nbsp;Marina Terekhova ,&nbsp;Katherine A. Carey ,&nbsp;Audrey F. Duff ,&nbsp;Maxim N. Artyomov ,&nbsp;Venkatakrishna R. Jala ,&nbsp;Rachel A. Idol ,&nbsp;Michael T. Bailey ,&nbsp;Mary C. Dinauer ,&nbsp;Richard J. Lamont ,&nbsp;Juhi Bagaitkar","doi":"10.1016/j.mucimm.2026.04.002","DOIUrl":"10.1016/j.mucimm.2026.04.002","url":null,"abstract":"<div><div>The leukocyte NADPH oxidase 2 (Nox2) is an important regulator of inflammatory responses, independent of its antimicrobial activity. Inactivating mutations in NOX2 cause chronic granulomatous disease (CGD), a severe immunodeficiency associated with recurrent infections and dysregulated neutrophilic inflammation. Recurrent oral ulcers, stomatitis, gingivitis, and other inflammatory issues affecting the oral mucosa have been observed in patients with CGD; however, the underlying mechanisms are not known. Here, we present evidence that the extensive inflammatory destruction of oral mucosal tissues observed in Nox2-deficient or <em>Cybb^KO</em> mice was not caused by impaired antimicrobial surveillance against oral pathobionts but instead resulted from a cell-intrinsic dysregulation of neutrophil inflammatory responses. Transcriptional and cellular profiling of oral tissues isolated from wild-type and <em>Cybb^KO</em> mice showed a dominant neutrophil signature, which was accompanied by a significant upregulation of several bone-resorbing, tissue-degrading inflammatory cytokines and a reduced expression of nuclear factor erythroid 2-related factor 2 (Nrf2) regulated genes. Mechanistically, hyperinflammatory responses were mitigated by restoring Nrf2 transcriptional activity using a synthetic agonist. Thus, our studies show that the Nox2 oxidase and derivative reactive oxygen species are crucial for balanced neutrophil recruitment and cell-intrinsic regulation of their inflammatory responses within oral tissues in an Nrf2-dependent manner.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100341"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654638","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":"S1P/S1PR3 axis drives epithelial dysfunction and type 2 inflammation in chronic rhinosinusitis with nasal polyps","authors":"Han Chen ,&nbsp;Lin Wang ,&nbsp;Lin Han ,&nbsp;Longgang Yu ,&nbsp;Xudong Yan ,&nbsp;Chunge Zheng ,&nbsp;Shunke Li ,&nbsp;Yibang Shen ,&nbsp;Zihui Dong ,&nbsp;Wenrui Tang ,&nbsp;Jisheng Zhang ,&nbsp;Yan Jiang","doi":"10.1016/j.mucimm.2026.03.004","DOIUrl":"10.1016/j.mucimm.2026.03.004","url":null,"abstract":"<div><div>Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by epithelial barrier dysfunction and type 2-dominant inflammation, yet the upstream regulatory mechanisms linking epithelial remodeling and immune activation remain poorly understood, and reliable biomarkers for eosinophilic CRSwNP (EOS CRSwNP) are limited. This study investigated the role of the sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) axis in epithelial barrier dysfunction and immune inflammation, and assess its potential as an adjunctive biomarker. S1P levels were significantly elevated in both serum and nasal tissues of CRSwNP patients, especially in the eosinophilic subtype, and correlated with disease severity and epithelial-mesenchymal transition (EMT) marker expression. In vitro experiments using human nasal epithelial cells (HNEpCs and primary HNECs) showed that S1P induced EMT and impaired barrier function predominantly through S1PR3. Pharmacological inhibition and lentiviral knockdown of S1PR3 attenuated these effects. Transcriptomic analysis identified PI3K-AKT signaling as a key downstream pathway mediating S1P/S1PR3-driven epithelial dysfunction. Multiplex immunofluorescence revealed increased S1PR3 expression in epithelial cells as well as in eosinophils and group 2 innate lymphoid cells (ILC2) in human nasal polyp tissues. In a murine nasal polyp model, pharmacological inhibition of S1PR3 attenuated polyp formation, restored epithelial junction proteins, reduced eosinophil and ILC2 infiltration, and suppressed Th2-associated cytokines (IL-4, IL-5, and IL-13). Moreover, serum S1P levels closely reflected tissue expression and disease severity, when combined with peripheral eosinophil percentage, improved diagnostic performance for identifying EOS CRSwNP. Collectively, these findings demonstrate that the S1P/S1PR3 axis links epithelial barrier dysfunction with type 2 immune inflammation in CRSwNP and may represent a promising therapeutic target and adjunctive biomarker for disease stratification.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100330"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434309","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":"Epithelial barrier DUOX2 serves as early immune defense in intestinal pathogen control","authors":"Maurice O’Mara ,&nbsp;Suisheng Zhang ,&nbsp;Claire Fergus ,&nbsp;Vincent P. Kelly ,&nbsp;Ulla G. Knaus","doi":"10.1016/j.mucimm.2026.04.004","DOIUrl":"10.1016/j.mucimm.2026.04.004","url":null,"abstract":"<div><div>Epithelial barriers constitute the first line of immune defense, preventing pathogen adherence, growth and entry through physical and chemical mechanisms. Essential to chemical defense are reactive oxygen species, usually provided by the phagocyte NADPH oxidase. DUOX2, a related oxidase, functions as sensor of the gut environment, and its dysregulation has been associated with inflammatory bowel disease. Here, we combine cell-based approaches with newly developed transgenic mice to explore how altering epithelial DUOX2 activity shapes host responses to intestinal bacteria including IBD-associated pathogens and to chemical colitis inducers. Although the pathogenic mechanisms of these bacteria differ, each triggered DUOX2 recruitment and transient H₂O₂ bursts in the vicinity of the pathogen during early, but not late, stages of infection. In vivo, epithelial DUOX2 acted as universal immune defense system without inducing or perpetuating intestinal inflammation. Our findings show that epithelial DUOX2 chemically undermines pathogen-induced niches, decreasing bacterial virulence and strengthening the barrier.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100343"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662937","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":"Indoor rewilding of laboratory mice recalibrates pulmonary mucosal immunity and mechanics","authors":"Mohamed Lala Bouali ,&nbsp;Amir Mohamed Kezai ,&nbsp;Marie-Josée Beaulieu ,&nbsp;Joanny Roy ,&nbsp;Papa Yaya Badiane ,&nbsp;Véronique Lévesque ,&nbsp;Luc Filion ,&nbsp;Luc Vallières ,&nbsp;Marie-Renée Blanchet ,&nbsp;Sébastien S. Hébert","doi":"10.1016/j.mucimm.2026.02.003","DOIUrl":"10.1016/j.mucimm.2026.02.003","url":null,"abstract":"<div><div>Laboratory mice raised under specific-pathogen-free (SPF) conditions experience restricted microbial and antigenic exposure, which favours an immature immune system and limits their translational value for respiratory research. While microbial enrichment in “dirty” mouse models restores immune maturation, its impact on integrated respiratory function and model transferability to human disease remains understudied. Here, we tested whether ecological exposure through indoor rewilding of SPF-reared mice could reshape immune complexity and recalibrate pulmonary physiology. Two-month-old female C57BL/6J mice were housed for three months under SPF or indoor-rewilding conditions and assessed for immune, mechanical, and systemic parameters. Rewilded mice exhibited expanded pulmonary immune subsets, increased dendritic-cell immune checkpoint, with TNF/IFN-γ activation coupled to regulatory IL-10 signaling. Despite sustained exposure, the alveolar-capillary barrier integrity was preserved. Functionally, respiratory oscillometry revealed improved pulmonary mechanics, including lower airway resistance, higher compliance, and reduced airway responsiveness to methacholine. Systemic cytokine analyses indicated compartmentalized pulmonary immune activation, maintaining an overall anti-inflammatory balance. Importantly, PRIA screening detected no reportable pathogens introduced during rewilding, while cecal shotgun metagenomics confirmed microbial enrichment. Together, these findings demonstrate that indoor rewilding reestablishes coordinated lung immune and mechanical homeostasis in SPF-reared mice, providing a safe and scalable model for studying human-like mucosal immunity and respiratory physiology with broad implications for preclinical respiratory research and therapeutic testing.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100322"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142887","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":"Mycobacterium tuberculosis preferentially infects specific macrophage subsets in primate granulomas during the early stages of tuberculosis","authors":"Davide Pisu ,&nbsp;Persis S. Sunny ,&nbsp;Molly L. Nelson ,&nbsp;Beth F. Junecko ,&nbsp;Roopa Venugopalan ,&nbsp;Mark A. Rodgers ,&nbsp;H. Jacob Borish ,&nbsp;Pauline Maiello ,&nbsp;Charles A. Scanga ,&nbsp;Philana Ling Lin ,&nbsp;JoAnne L. Flynn ,&nbsp;David G. Russell ,&nbsp;Joshua T. Mattila","doi":"10.1016/j.mucimm.2026.02.002","DOIUrl":"10.1016/j.mucimm.2026.02.002","url":null,"abstract":"<div><div>Tuberculosis (TB) is caused by <em>Mycobacterium tuberculosis</em> (Mtb) infection and defined by formation of granulomas, immune aggregates that can restrict or support bacterial replication. Macrophages are fundamental components of granulomas and TB pathogenesis, yet their population structure and functional diversity is incompletely understood. The interaction between macrophages and Mtb <em>in vivo</em>, including which cell subsets are infected and how they respond to colonization, is a major determinant of disease outcome. Here, we profiled lung tissue and granulomas from Mtb-infected cynomolgus macaques, an animal model that closely recapitulates human TB, to define macrophage biology in the early stage of infection. We identified distinct subsets, including embryonic-origin tissue resident alveolar macrophages (AMs), monocyte-derived AMs, and interstitial macrophages with distinct spatial localization in granulomas. Tissue-resident AMs and a novel macrophage subset undergoing epithelial-to-mesenchymal transition were the most frequently infected cells in lung tissue. Mtb-infected cells specifically expressed immune-related and migration-associated genes, suggesting that Mtb induces or exploits these pathways in early infection as a survival strategy <em>in vivo</em>. Our findings highlight the complex interplay between macrophage heterogeneity and functional states that serve as a driver of susceptibility to Mtb infection and TB progression.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100321"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125738","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":"Metabolic regulation of macrophage-tissue interactions in the lung","authors":"Tim Willinger","doi":"10.1016/j.mucimm.2026.03.010","DOIUrl":"10.1016/j.mucimm.2026.03.010","url":null,"abstract":"<div><div>Macrophages play important roles in lung homeostasis and disease by interacting with their surrounding tissue microenvironment. Accordingly, macrophage metabolism and local metabolites shape immune responses in the lung. Here, I review the metabolic regulation of lung macrophages and regulation of lung immunity by macrophage metabolism in the context of lung injury, host defense, and tissue repair. First, the intrinsic regulation of macrophages by intracellular metabolism is discussed with a focus on how macrophages adapt to the metabolic milieu of the lung in steady state and when lung homeostasis is disturbed. Second, the extrinsic regulation of macrophages and lung immunity by extracellular metabolites is reviewed. Specifically, I present how metabolites acting on lung macrophages control their function. In addition, I discuss how metabolites produced by macrophages impact lung function. Finally, I provide an overview of future areas of research related to the regulation of lung macrophages by tissue-derived metabolites.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100336"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504414","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":"EPICERTIN, an engineered variant of cholera toxin B subunit, promotes survival and a pro-remodeling macrophage phenotype for mucosal healing in colitis","authors":"Noel Verjan Garcia ,&nbsp;Jimmy Fernando Cifuentes ,&nbsp;Micaela A. Reeves ,&nbsp;Jae Yeon Hwang ,&nbsp;Juw Won Park ,&nbsp;Susan Galandiuk ,&nbsp;Nobuyuki Matoba","doi":"10.1016/j.mucimm.2026.01.013","DOIUrl":"10.1016/j.mucimm.2026.01.013","url":null,"abstract":"<div><div>EPICERTIN, a modified cholera toxin B subunit (CTB), facilitates mucosal healing in preclinical colitis models, but its anti-inflammatory mechanisms remain unclear. Here, we investigated EPICERTIN’s effects on macrophages. In a dextran sulfate sodium-induced colitis mouse model, oral administration of EPICERTIN reduced neutrophil infiltration and increased CX3CR1⁺MHCII^lo/- (M2-like) over CX3CR1⁺MHCII^hi (M1-like) macrophages in the colon lamina propria. This was concurrent with upregulation of colony-stimulating factor 2 (<em>Csf2</em>) and growth factors (<em>Egf</em>, <em>TgfA</em>, <em>Fgf</em>, <em>Pdgf</em>) involved in mucosal remodeling. Similarly, in colon tissue from a human with active colitis, EPICERTIN significantly upregulated <em>CSF2</em> and tissue repair-associated genes while downregulating proinflammatory genes (<em>IL1B</em>, <em>IL6ST</em>). In vitro, EPICERTIN promoted macrophage survival under serum-free conditions, whereas CTB induced apoptosis in murine RAW264.7 cells, peritoneal macrophages, and human THP-1 cells. Remarkably, EPICERTIN protected macrophages from apoptosis induced by chemical ER-stressors or lipopolysaccharides. Additionally, EPICERTIN downregulated cell surface molecules HLA-DR, CD14, CD80, and CD86 in THP-1 cells and modestly upregulated chemokines and proinflammatory cytokines genes as well as <em>TGFB1</em> in human PBMC-derived macrophages. In contrast, CTB strongly increased proinflammatory genes and activation markers. These findings indicate that EPICERTIN promotes macrophage homeostasis by inducing a less inflammatory, pro-remodeling phenotype, whereas CTB may trigger activation-induced cell death.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1922-1936"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132280","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":"Fibroblasts sense commensal-derived metabolites and regulate group 2 innate lymphoid cells-dependent defense in the stomach","authors":"Naoko Satoh-Takayama ,&nbsp;Yuko Shigeno ,&nbsp;Ritsu Nagata ,&nbsp;Tamotsu Kato ,&nbsp;Yumiko Nakanishi ,&nbsp;Tomoko Kageyama ,&nbsp;Naoko Tachibana ,&nbsp;Ayumi Ito ,&nbsp;Yoshimi Benno ,&nbsp;Hiroshi Ohno","doi":"10.1016/j.mucimm.2026.01.007","DOIUrl":"10.1016/j.mucimm.2026.01.007","url":null,"abstract":"<div><div>Group 2 innate lymphoid cells (ILC2s) contribute to mucosal homeostasis and initiate immune responses against gastrointestinal pathogens, including those that target the stomach. However, the role of commensal bacteria in promoting stomach immunity is unknown. Here, we report that YL27, a commensal bacterium from the family <em>Muribaculaceae</em>, modulates stomach ILC2s and their associated immune effector functions. Activation of stomach ILC2s was initiated by a subset of IL-33-producing fibroblasts in response to acetate, a metabolite of YL27, via its receptor GPR43. ILC2s-derived IL-13 was required for the induction of Muc1 expression in the epithelium and contributed to protection from <em>H. pylori</em> infection. Thus, these findings demonstrate that ILC2s-mediated immune responses in the stomach are initiated by interactions between commensal bacteria and fibroblasts, and highlight the role of commensals in the innate response to pathogenic bacteria for the first line of mucosal defense.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1862-1874"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137769","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":"Single cell atlas of lung-resident innate lymphoid cells shows impact of age and dysbiosis on epigenetic and transcriptomic programming","authors":"Madeline Bonfield ,&nbsp;Jerilyn Gray ,&nbsp;Alicia Ramiriqui ,&nbsp;Joseph Stevens ,&nbsp;Uday Pandey ,&nbsp;Laura Canaday ,&nbsp;H.Alex Feldman ,&nbsp;William J Zacharias ,&nbsp;Leah Kottyan ,&nbsp;Stephen N. Waggoner ,&nbsp;Hitesh Deshmukh ,&nbsp;Shelby Steinmeyer","doi":"10.1016/j.mucimm.2026.01.004","DOIUrl":"10.1016/j.mucimm.2026.01.004","url":null,"abstract":"<div><div>The mechanisms underlying innate lymphoid cell (ILC) development and function in the neonatal lung remain incompletely defined. ILCs are critical mediators of early-life innate immune responses in the lung. Dysregulation of ILC homeostasis has both immediate and long-lasting effects on lung health. We generated single-cell transcriptomic and epigenetic datasets from the lungs of neonatal and young adult</div><div>mice that includes subsets of type 1 (natural killer, NK cells) type 2 (ILC2) and type 3 (ILC3) cells. These datasets include mice subjected to early life antibiotic-induced dysbiosis, thereby modeling a common perturbation of the developing immune system in humans. Analysis of cell-cell communication and gene regulation in these datasets reveals underappreciated aspects of lung ILC biology, including marked interleukin-4 (IL-4) signaling in neonatal lung ILC2. This data represents a valuable resource for hypothesis generation regarding the molecular regulation of ILC gene expression and function in the neonatal lung.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1835-1847"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003719","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}