Mucosal Immunology最新文献

{"title":"IL-11 acts as an alarmin-like pro-inflammatory mediator regulating mucosal responses during helminth infection","authors":"Pedro H. Gazzinelli-Guimaraes ,&nbsp;Pablo Bara-Garcia ,&nbsp;Jonah Kupritz ,&nbsp;Fabricio Marcus Silva Oliveira ,&nbsp;Camila Queiroz-Glauss ,&nbsp;Byunghyun Kang ,&nbsp;Michelle Makiya ,&nbsp;Thomas B. Nutman","doi":"10.1016/j.mucimm.2026.01.005","DOIUrl":"10.1016/j.mucimm.2026.01.005","url":null,"abstract":"<div><div>Lung-trafficking helminth larvae drive an early pulmonary neutrophilic inflammation prior to the establishment of the hallmark Type 2 immune response. While IL-11 is known to play crucial roles in chronic inflammatory responses, its role in the mucosal immunity to helminth parasites has not been assessed to date. In a mouse model for <em>Ascaris</em> infection, we observed elevated IL-11 levels in lung tissue that strikingly correlated with parasite burden. Single-cell molecular and phenotypic analyses, combined with confocal and RNAscope spatial imaging, identified lung epithelial cells and peribronchial stromal cells, including myofibroblasts and smooth muscle cells, as important sources of IL-11 in naïve and <em>Ascaris-</em>infected lungs. In the absence of IL-11 signaling, using IL-11Rα1-deficient mice infected with <em>Ascaris</em>, we noted a marked reduction in lung neutrophil influx and decreased levels of neutrophil-associated mediators (CXCL-1 and G-CSF). Conversely, intranasal administration of recombinant IL-11 induced high levels of G-CSF and CXCL-1 and enhanced mucosal inflammation in the lungs. To confirm direct effect of IL-11 in regulating neutrophil-associated markers we showed that <em>in vitro</em> stimulation with recombinant IL-11 drove IL-6 and G-CSF production in fibroblasts, and CXCL-1 in epithelial cells. These findings suggest that IL-11 acts as a pro-inflammatory mediator that orchestrates the early neutrophil-driven inflammation during acute helminth infection, unraveling a critical role of IL-11 in pathogenic inflammatory responses.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1848-1861"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998530","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":"Integrated human and mouse single-cell profiling reveals immune-stromal niche driving silicosis","authors":"Christina Begka ,&nbsp;Matthew Macowan ,&nbsp;Bailey Cardwell ,&nbsp;Anh Thu Dang ,&nbsp;Carmel P Daunt ,&nbsp;Roxanne Chatzis ,&nbsp;Hayley Barnes ,&nbsp;David Pilcher ,&nbsp;Ian Glaspole ,&nbsp;Ryan F Hoy ,&nbsp;Nicola L Harris ,&nbsp;Glen P Westall ,&nbsp;Benjamin J Marsland","doi":"10.1016/j.mucimm.2026.01.003","DOIUrl":"10.1016/j.mucimm.2026.01.003","url":null,"abstract":"<div><div>Silicosis is an inflammation-driven pulmonary fibrosis caused by occupational inhalation of silica particles. Macrophages are crucial in silicosis pathology, yet their interaction with stromal cells in orchestrating fibrosis progression remains poorly understood. Single-cell RNA sequencing (scRNAseq) of whole-lung lavages from silicosis patients identified the expansion of an intermediate <em>CCL2</em>-hi monocyte-like macrophage (MLM) cluster that further differentiated into inflammatory <em>IL1B</em>-hi and pre-fibrotic <em>SPP1</em>-hi (osteopontin) subsets. SPP1-hi MLMs showed enrichment for tissue remodelling (<em>SPP1</em>, <em>CHI3L1</em>, <em>MMP14</em>, <em>COL6A1</em>), oxidative stress (<em>GCLC</em>, <em>TXN</em>, <em>PRDX1</em>), and bio-mineralisation genes (<em>GLA</em>, <em>CA2</em>, <em>CTSK</em>). To explore immune–stromal dynamics, we developed a site-specific silicosis mouse model with a miniture bronchoscope. Mouse scRNAseq analysis and cell–cell communication modelling identified novel neutrophil subsets, reprogrammed alveolar type 2 epithelial cells, and two <em>Sfrp1</em>-hi/<em>Spp1</em>-hi fibroblast subsets involved in crosstalk with MLMs. These data identify key components of the silicotic niche and predict targetable interactions within the immune–stromal axis for ameliorating disease.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1822-1834"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952615","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":"Short-course intranasal LAT9997 therapy limits post-influenza bacterial pneumonia by recalibrating lung immunity","authors":"Alison C. West ,&nbsp;Christopher M. Harpur ,&nbsp;Maggie Lam ,&nbsp;Rebecca L. Ambrose ,&nbsp;Christopher J. Hodges ,&nbsp;Stuart Mudge ,&nbsp;David Kenley ,&nbsp;Andrew J. Gearing ,&nbsp;Michelle D. Tate","doi":"10.1016/j.mucimm.2026.01.008","DOIUrl":"10.1016/j.mucimm.2026.01.008","url":null,"abstract":"<div><div>Secondary bacterial pneumonia causes substantial morbidity and mortality following influenza A virus (IAV) infection, yet no therapies exist that address the underlying immune dysfunction and epithelial damage that predispose to bacterial superinfection. Here, we demonstrate that short-course intranasal treatment with LAT9997, a synthetic peptide derived from human growth hormone, protects against severe IAV infection and subsequent <em>Streptococcus pneumoniae</em> superinfection. Significantly, just two intranasal doses administered on days 1 and 2 post-IAV infection, with no further treatment, improved survival from 0% to 85%, reduced bacterial burden in the airways, and markedly attenuated lung pathology. Mechanistically, LAT9997 selectively suppressed epithelial AKT Ser473 phosphorylation, rebalancing infection-induced signalling to reduce viral dissemination, limit lung damage, and preserve barrier integrity during the viral phase. This early intervention established a protective airway immune environment characterized by preserved alveolar macrophages, restrained neutrophil recruitment, and reduced inflammatory mediators. During subsequent bacterial challenge, innate immune cells displayed phenotypic markers of controlled activation, including enhanced neutrophil viability, reduced inflammatory surface markers, and restrained protease activity, occurring without broad alterations in cell numbers. These findings provide proof-of-concept that brief, host-directed therapy during acute viral infection can durably prevent post-viral bacterial pneumonia by modulating lung immunity and preserving barrier integrity.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1875-1888"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046839","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":"Corrigendum to “The C-type lectin receptor MINCLE interferes with eosinophil function and protective intestinal immunity in Strongyloides ratti-infected mice”. [Mucosal Immunol. 18(1) (2025) 220–231]","authors":"Lara Linnemann ,&nbsp;Jennifer Antwi-Ekwuruke ,&nbsp;Vinayaga Gnanapragassam ,&nbsp;Corinna Bang ,&nbsp;Malte Rühlemann ,&nbsp;Jürgen Ruland ,&nbsp;Wiebke Hartmann ,&nbsp;Lennart Heepmann ,&nbsp;Sara Dörken ,&nbsp;Saleh M. Yunus ,&nbsp;Birte Viebrock ,&nbsp;Annette Schlosser ,&nbsp;Bernd Lepenies ,&nbsp;Minka Breloer","doi":"10.1016/j.mucimm.2026.03.001","DOIUrl":"10.1016/j.mucimm.2026.03.001","url":null,"abstract":"","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Page 1954"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463691","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 transcriptome analysis reveals the association between ketone body synthesis and morphogenic profile of intestinal epithelia in neonatal mice","authors":"Kyoko Matsuki ,&nbsp;Taiki Sakaguchi ,&nbsp;Mari Murakami ,&nbsp;Ryu Okumura ,&nbsp;Hisako Kayama ,&nbsp;Maika Yamashita ,&nbsp;Yu-Chen Liu ,&nbsp;Daisuke Okuzaki ,&nbsp;Keita Takayama ,&nbsp;Masafumi Kamiyama ,&nbsp;Hiroomi Okuyama ,&nbsp;Kiyoshi Takeda","doi":"10.1016/j.mucimm.2025.12.005","DOIUrl":"10.1016/j.mucimm.2025.12.005","url":null,"abstract":"<div><div>The intestinal epithelium undergoes robust maturation postnatally, yet its early-life characteristics remain poorly understood. Using single-cell RNA sequencing, we analyzed intestinal epithelial cells from neonatal (10-day-old) and juvenile (21-day-old) mice reared under both specific pathogen-free and germ-free conditions. Among the various cell types comprising the intestinal epithelia, we found that enterocytes, in particular, exhibit markedly different features between these stages. Enterocytes of neonatal mice show reduced expression of secretory host defense-related genes independently of microbial colonization. These genes are upregulated in juvenile enterocytes in a microbiota-independent manner. Conversely, neonatal enterocytes display upregulation of ketogenesis-related genes, which correlates with high expression of genes contributing to cell morphogenesis rather than serving primarily as an energy source. These findings provide novel insights into early-life maturation of intestinal epithelia offering implications for understanding neonatal intestinal pathologies.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1783-1798"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889695","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":"Distinct phenotypes and repertoires of bronchoalveolar and airway mucosal T cells in health and allergic asthma","authors":"Rod A. Rahimi ,&nbsp;Neal P. Smith ,&nbsp;Amandine Selle ,&nbsp;Roya Best ,&nbsp;Sidney Martin ,&nbsp;Elizabeth Tuttle ,&nbsp;Wamia Said ,&nbsp;Nandini Samanta ,&nbsp;Morris F. Ling ,&nbsp;Benjamin D. Medoff ,&nbsp;Alexanda-Chloé Villani ,&nbsp;Andrew D. Luster","doi":"10.1016/j.mucimm.2026.01.001","DOIUrl":"10.1016/j.mucimm.2026.01.001","url":null,"abstract":"<div><div>T cells play a central role in host protection against respiratory pathogens, but a maladaptive T cell response can lead to pulmonary diseases. Previous studies have examined T cells from the lungs captured via bronchoalveolar lavage (BAL), endobronchial brushings, or biopsies. However, whether these different approaches are capturing distinct T cell phenotypes and/or clonotypes remains unclear. Here, using single cell RNA- and T cell receptor (TCR)-sequencing, we report unique phenotypes and clonotypes of T cells isolated via BAL versus endobronchial brushings in healthy controls (HCs) and allergic asthmatics (AAs). The most significant difference in T cell subset abundance between AAs and HCs was the enrichment of CD4 T helper type 2 (T_H2) cells when comparing endobronchial brush samples (OR = 20.8, P = 0.004), but not when examining BAL (OR = 1.8, P = 0.38), indicating differences in the T cell subsets captured from the BAL versus airway mucosa. In further support of this observation, comparing the BAL and brush T cells across all subjects revealed an up-regulation of resident-memory T (T_RM) cell markers (i.e. <em>ITGAE, CD69</em>) in brush T cells in both CD4 and CD8 lineages. In contrast, BAL CD8 and CD4 T cells exhibited an enriched type I and II interferon signature compared to brush T cells. We validated these findings by generating an independent cohort from publicly available single cell RNA-sequencing data of BAL and brush T cells. Lastly, leveraging the paired samples from our derivation cohort, we performed TCR repertoire analysis, revealing that brush T cells contained expanded TCR clones that were in low abundance or absent in the BAL. Expanded T cell clones from the brush expressed high levels of T_RM cell markers, suggesting the airway mucosa is enriched for T_RM cells with unique TCR specificity. In sum, sampling T cells via BAL versus airway brushings yielded distinct T cell phenotypes and clonotypes with important implications for future research in lung immunology.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1799-1807"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948816","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":"ILC3s mediate intestinal immune-epithelial interactions via TGF-β1 activation","authors":"Diana Coman ,&nbsp;John W. Bassett ,&nbsp;Isabelle Coales ,&nbsp;Ainize Peña-Cearra ,&nbsp;Emily Read ,&nbsp;Emma H. Kromann ,&nbsp;Daniel Brice ,&nbsp;Zuzanna Łukasik ,&nbsp;Helena Paidassi ,&nbsp;Matthew R. Hepworth ,&nbsp;Robin J. Dart ,&nbsp;Mark A. Travis ,&nbsp;Jenny Mjösberg ,&nbsp;Luke B. Roberts ,&nbsp;Joana F. Neves","doi":"10.1016/j.mucimm.2025.11.013","DOIUrl":"10.1016/j.mucimm.2025.11.013","url":null,"abstract":"<div><div>Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract. It is characterised by epithelial and immunological dysfunctions, including alterations in populations of Innate Lymphoid Cells (ILCs), including tissue-resident RORγt-expressing Group 3 ILCs (ILC3s). ILC3s contribute to the maintenance of intestinal homeostasis by closely interacting with both the epithelium and adaptive immune cells. Here, we reveal that murine and human ILC3s modulate these interactions through Transforming Growth Factor-Beta 1 (TGF-β1), a pleiotropic cytokine secreted in an inactive form. We show that ILC3s synthesise and activate latent TGF-β1 through mechanical and proteolytic pathways. ILC3s aid the induction of FoxP3⁺ regulatory T cells via TGF-β1 and promote a regenerative transcriptional signature in intestinal epithelial cells. The downstream impact of ILC3-derived TGF-β1 is conserved between mouse and humans, but the TGF-β1 activators expressed by ILC3 differ between the species. In IBD, where ILC3s are reduced in the inflamed intestinal regions, TGF-β1-production and activation machinery remains intact in ILC3s, suggesting this pathway is functional in disease and could be targeted to enhance intestinal homeostasis through promotion of epithelial regeneration and induction of regulatory T cells.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1735-1748"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636096","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":"Regulatory T cells protect against aberrant remodeling in a mouse model of pulmonary fibrosis","authors":"Aditi Murthy ,&nbsp;Luis R. Rodríguez ,&nbsp;Willy Roque Barboza ,&nbsp;Yaniv Tomer ,&nbsp;Sarah Bui ,&nbsp;Paige Carson ,&nbsp;Thalia Dimopoulos ,&nbsp;Swati Iyer ,&nbsp;Katrina Chavez ,&nbsp;Charlotte H. Cooper ,&nbsp;Jeremy B. Katzen ,&nbsp;Michael F. Beers","doi":"10.1016/j.mucimm.2025.12.004","DOIUrl":"10.1016/j.mucimm.2025.12.004","url":null,"abstract":"<div><div>Regulatory T (Treg) cells are well recognized for their role in immune regulation; however, their role in tissue regeneration is not fully understood. This study demonstrates such a role of Tregs in a published preclinical murine model of spontaneous pulmonary fibrosis (PF) expressing a human PF related mutation in the Surfactant Protein-C (SP-C) gene (SFTPC^I7³^T). Genetic crosses of SP-C^I7³^T mice with Foxp3^GFP and Foxp3^DTR lines were utilized to study Treg behavior during PF development. We found that FoxP3+ Tregs accumulate during the transition from inflammation to fibrogenesis, peaking at 21–28 days after mutant Sftpc^I7³^T induction localizing to both perivascular and distal fibrotic lung regions. Diphtheria toxin mediated ablation of Tregs at 17 days worsened fibrosis and increased levels of TGFβ and inflammatory cytokines. Tregs expressed Th2 markers (Gata3+) and elaborated factors including amphiregulin (Areg) and Osteopontin (Spp1). Reductionist experiments showed that lung Tregs enhanced organoid formation when co-cultured with alveolar epithelial cells and adventitial fibroblasts, an effect size mimicked using Areg and Spp1 in combination. Our findings demonstrate that immune-mesenchymal-epithelial signaling crosstalk is present in the distal lung wherein Tregs play a protective role by limiting fibrosis and promoting tissue repair, highlighting their broader function beyond immune modulation in lung injury.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1769-1782"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857240","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":"Natural Killer T follicular helper cell function permits germinal centre entry in nasal associated lymphoid tissue","authors":"Isabelle Montgomerie ,&nbsp;Jessica Cotterell ,&nbsp;Theresa E. Pankhurst ,&nbsp;Kaileen R. Button ,&nbsp;Cynthia Morgan ,&nbsp;Andrew J. Marshall ,&nbsp;Gavin F. Painter ,&nbsp;Benjamin J. Compton ,&nbsp;Lisa M. Connor","doi":"10.1016/j.mucimm.2025.11.011","DOIUrl":"10.1016/j.mucimm.2025.11.011","url":null,"abstract":"<div><div>Germinal centres (GCs) in mucosal tissues such as the nasal associated lymphoid tissue (NALT) generate high-affinity antibodies critical for protective, and in some cases, sterilising immunity. Therefore, initiation of GCs at the respiratory mucosa is of tremendous clinical significance in the development of mucosal vaccines. However, GC initiation in NALT is limited in part by a scarcity of CD4⁺ T follicular helper (T_FH) cells, and the tolerogenic environment in the NALT. Here, we identify a critical role for Natural Killer T (NKT) cells with a follicular helper-like phenotype (NKT_FH) in driving NALT GC formation. Unlike their systemic counterparts, mucosal NKT cells evade anergy after repeated stimulation and remain poised to provide early cognate B cell help to CD1d-presented antigens. We show that NKT_FH provide IL-21, allowing for GC recruitment and functionally substituting for a pre-expanded CD4⁺ T_FH pool. These findings reveal a previously unrecognised NKT-dependent mechanism of GC seeding in the NALT and suggest that inclusion of an NKT cell agonist into intranasal vaccines could overcome GC entry bottlenecks and enhance high-affinity antibody responses.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1703-1717"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596917","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":"Trained ILC2 prevent IL-17-associated lung injury during helminth infection through a serotonin-dependent mechanism","authors":"Ulrich Membe Femoe ,&nbsp;Fungai Musaigwa ,&nbsp;Imani Nicolis ,&nbsp;Li-Yin Hung ,&nbsp;Camila Napuri ,&nbsp;Chinwekele Uzoije ,&nbsp;Heather L. Rossi ,&nbsp;Cailu Lin ,&nbsp;Heidi Winters ,&nbsp;Danielle R. Reed ,&nbsp;Juan Manuel Inclan-Rico ,&nbsp;De’Broski R. Herbert","doi":"10.1016/j.mucimm.2026.01.002","DOIUrl":"10.1016/j.mucimm.2026.01.002","url":null,"abstract":"<div><div>Type 2 cytokine release promotes wound healing and helminth clearance, but it remains unclear whether group 2 innate lymphocytes (ILC2s) and T-helper 2 cells (T_H2) cells have functionally distinct roles during anamnestic immunity. This study demonstrates that ILC2 can prevent re-infection and limit tissue injury caused by the helminth <em>Nippostrongylus brasiliensis (Nb)</em>. T_H2 cells were necessary during initial antigen encounter but dispensable for early pathogen clearance and lung repair after ILC2 priming. Upon re-infection, trained ILC2 selectively blocked interleukin (IL)-17+ γδT cell expansion and infection-induced lung injury through an Amphiregulin (<em>Areg</em>)-independent mechanism. Trained ILC2s had a distinct metabolic gene expression profile marked by elevated tryptophan hydroxylase 1(<em>Tph1</em>) and pulmonary serotonin levels were largely ILC2-dependent. Surprisingly, serotonin prevented IL-17-associated lung hemorrhage irrespective of parasite load. We propose that T_H2-ILC2 interactions drive pathogen control, but ILC2 distinctly control lung tissue repair through serotonin.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 2","pages":"Pages 1808-1821"},"PeriodicalIF":7.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145945195","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}