Journal of Leukocyte Biology最新文献

{"title":"The lung tells eosinophils who to become.","authors":"Yuki Moritoki, Shigeharu Ueki","doi":"10.1093/jleuko/qiag135","DOIUrl":"https://doi.org/10.1093/jleuko/qiag135","url":null,"abstract":"","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocyte-Derived Dendritic Cell Activation Is Broadly Conserved Across Immune Phenotype-Specific Ovarian Tumor Lysate Pools, With Donor-Associated Variation in Response Magnitude.","authors":"Emilija Paberalė, Yasmine Hassan Mohamed Rezk, Jan Aleksander Kraśko, Karolina Suveizdė, Vita Pašukonienė, Agata Mlynska","doi":"10.1093/jleuko/qiag134","DOIUrl":"https://doi.org/10.1093/jleuko/qiag134","url":null,"abstract":"<p><p>Whether ex vivo monocyte-derived dendritic cell responses are shaped more by tumor immune context or donor-associated variation remains unclear. Monocyte-derived dendritic cells from nine healthy female donors were exposed for 8 h to three lysate pools generated from 27 high-grade serous ovarian tumors classified as immune-desert, immune-excluded, or immune-inflamed. Individual lysates showed phenotype-associated chemokine differences. The three pooled stimulation conditions elicited broadly conserved dendritic cell maturation responses and shared inflammatory transcriptional programs, with limited gene- and pathway-level differences. Permutational multivariate analysis attributed ≈58% of global transcriptional variance to donor identity (P = 0.001), whereas pooled lysate condition accounted for ≈4%, which was not significant (P = 0.756). Response magnitude varied continuously across donors and showed exploratory associations with baseline pathway activity in immature dendritic cells. Under the tested conditions, early monocyte-derived dendritic cell activation was broadly shared across the three lysate pools, while the transcriptional response magnitude was more strongly associated with donor identity.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The chitinase-microbiota axis: connecting innate immunity, microbial ecology, and mucosal homeostasis.","authors":"Lucia Malaguarnera","doi":"10.1093/jleuko/qiag130","DOIUrl":"https://doi.org/10.1093/jleuko/qiag130","url":null,"abstract":"<p><p>Chitinases and chitinase-like proteins are evolutionarily conserved molecules increasingly recognized as components of biological networks linking environmental exposure, innate immunity, tissue organization, and host-microbial interactions. Mammalian chitinases include the catalytically active chitotriosidase (CHIT1) and acidic mammalian chitinase (CHIA/AMCase), alongside nonenzymatic chitinase-like proteins such as chitinase-3-like protein 1 (CHI3L1/YKL-40), which exert distinct but interconnected functions. Host chitinases and microbial chitinolytic systems may converge in environmental chitin processing, whereas CHI3L1 can influence epithelial-microbial interactions and mucus-associated microbial organization through nonenzymatic mechanisms. Environmental exposure and host genetic variability add further complexity: changes in exposure to microorganisms and chitin-containing organisms may modify chitinase-related pathways, while functional variants in CHIT1 and CHIA alter host chitinolytic capacity. However, their consequences for human microbial ecology remain incompletely defined. CHI3L1 also has established functions in neuroinflammatory and astroglial responses, raising the possibility of convergence with microbiota-dependent gut-brain communication, although a direct chitinase-microbiota-brain pathway has not been demonstrated. Here, we propose a multidimensional chitinase-microbiota axis integrating environmental chitin exposure, host and microbial chitinolytic activity, innate immune signaling, epithelial-microbial interactions, and tissue remodeling. We distinguish experimentally established mechanisms from emerging or hypothetical connections and identify critical gaps for testing causal relationships across mucosal, metabolic, and neuroimmune compartments. Reframing chitinases and chitinase-like proteins as context-dependent components of host-microbial ecosystems may provide a mechanistic framework for investigating inflammatory, metabolic, and neuroimmune diseases and defining future biomarker and therapeutic opportunities.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"118 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolite-mediated crosstalk between neutrophils, commensal bacteria, and dendritic cells is associated with intestinal immune responses.","authors":"Sun-Hwa Kim, Jun-Kyu Kim, Yu-Bin Lee, Hyeung-Wook Shin, Seong-Su Choi, Minsang Shin, Soo-Jung Jung, Chang-Won Hong","doi":"10.1093/jleuko/qiag123","DOIUrl":"10.1093/jleuko/qiag123","url":null,"abstract":"<p><p>The intestinal immune system relies on coordinated interactions between innate immune cells and commensal bacteria. How metabolites integrate host-microbe communication in the gut remains incompletely understood. Using neutrophil activation assays, bacterial chemotaxis analysis, short-chain fatty acid profiling, and imaging of inflamed intestinal tissue, we examined how neutrophil-derived metabolites regulate commensal behavior and immune cell function. Activated neutrophils released lactate, which was associated with selective chemotaxis of commensal Escherichia coli but not pathogenic Acinetobacter or Salmonella. This response required bacterial lactate dehydrogenase, suggesting that lactate metabolism may contribute to commensal localization within the intestinal mucosa. Commensal-derived short-chain fatty acids suppressed neutrophil activation by inhibiting neutrophil extracellular trap formation and reactive oxygen species generation, consistent with a potential feedback mechanism that may attenuate neutrophil activation. Neutrophil-derived soluble factors were associated with phenotypic changes in dendritic cells, as reflected by increased dendrite formation and modest elevation of major histocompatibility complex class II expression. Imaging revealed close spatial proximity between neutrophils and dendritic cells within inflamed villi, supporting spatial association consistent with potential crosstalk in vivo. These findings are consistent with a model of metabolite-mediated communication in which neutrophil-derived lactate may attract commensal bacteria, commensal-derived metabolites restrain neutrophil effector activity, and neutrophil-derived soluble factors are associated with phenotypic changes in dendritic cells rather than definitive functional maturation, collectively suggesting potential contributions to immune regulatory processes within the intestinal mucosa.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Δ9-Tetrahydrocannabinol exposure shifts eosinophil and macrophage transcriptional programs toward an anti-inflammatory phenotype in helminth infection.","authors":"Jennell Jennett, Martin Olmos, Ka Man Lam, Sarah Midou, Nicholas V DiPatrizio, Meera G Nair","doi":"10.1093/jleuko/qiag131","DOIUrl":"10.1093/jleuko/qiag131","url":null,"abstract":"<p><p>Cannabis use is increasing globally, yet the immunological effects of Δ9-tetrahydrocannabinol, the main intoxicating component of cannabis, remain incompletely understood. Given prior evidence that endocannabinoid signaling influences helminth immunity and type 2 inflammation, we investigated how sustained Δ9-tetrahydrocannabinol exposure alters immune responses to the helminth Nippostrongylus brasiliensis, which infects the lung and small intestine of mice. C57BL/6J mice were treated with Δ9-tetrahydrocannabinol (5 mg/kg/d) or vehicle for 14 d prior to helminth infection and assessed for parasite burden, innate immune cell and T cell responses, and transcriptional changes in lung eosinophils and macrophages. Δ9-Tetrahydrocannabinol exposure did not significantly alter infection-associated weight loss or helminth burden; however, Δ9-tetrahydrocannabinol selectively restrained infection-induced circulating eosinophils and monocytes while increasing regulatory T cells. T cell activation assays showed reduced TNFα and IFNγ secretion in splenocytes from Δ9-tetrahydrocannabinol-treated infected mice. Bulk RNA sequencing showed that Δ9-tetrahydrocannabinol shifted lung eosinophils and CD11c+ lung macrophage-enriched cells from inflammatory, fibrotic, and costimulatory pathways toward stress and metabolic-adaptive transcriptional programs. Within the infected macrophage-enriched population, Δ9-tetrahydrocannabinol reduced CD80 expression while increasing MHC class II and antigen presentation-associated genes, suggesting a potential shift in macrophage-mediated T cell activation. Consistent with altered inflammatory and tissue remodeling-associated programs, immunofluorescent staining showed that Δ9-tetrahydrocannabinol mitigated infection-associated loss of lung collagen. Collectively, these findings indicate that Δ9-tetrahydrocannabinol reshapes the immune response to helminth infection by restraining innate and T cell effector responses while altering lung eosinophil and macrophage activation programs.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The light side of mast cell degranulation: delivering macrophage repair through molecular condensates.","authors":"Alejandro Schcolnik-Cabrera, Rommel Chacón-Salinas","doi":"10.1093/jleuko/qiag125","DOIUrl":"10.1093/jleuko/qiag125","url":null,"abstract":"<p><p>Mast cell (MC) degranulation is commonly viewed as the rapid release of preformed inflammatory mediators into the extracellular environment. In a recent study published in the Journal of Experimental Medicine, Salm et al. described a more spatially controlled form of MC communication following sterile peritoneal injury. Sensory neurons activated MCs through substance P signaling, promoting the release of extracellular granules that persisted as membraneless biomolecular condensates. These condensates, enriched in more than 200 proteins, remained associated with the surface of large peritoneal macrophages (LPMs), where they contributed to rapid macrophage aggregation through the scavenger receptor MARCO and promoted a repair-like phenotype at the injury site. Lattice light sheet microscopy further revealed F-actin-containing cytonemes that captured condensates from the MC surface and distributed them to surrounding macrophages. Importantly, disruption of this process impaired condensate dispersion, LPM recruitment, and wound healing. The study expands the conventional view of MC degranulation beyond the release of inflammatory soluble mediators by showing that released granules can remain organized and be actively positioned within injured tissue, creating a localized communication system between sensory neurons, MCs, and macrophages.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intoxication, inflammaging, and injury: my journey through leukocyte biology.","authors":"Rachel H McMahan, Mashkoor A Choudhry, Juan-Pablo Idrovo, Rebecca L McCullough, Elizabeth J Kovacs","doi":"10.1093/jleuko/qiag121","DOIUrl":"10.1093/jleuko/qiag121","url":null,"abstract":"<p><p>Senior author E.J.K. writes: As a scientist, teacher, research mentor, and mom, I asked myself, \"what is my legacy?\" Legacies usually have numbers associated with them. When asked this question in the past, I summed my accomplishments in terms of who, not what. First and foremost, I have my daughter, Cathy, and then scores of spectacular lab trainees (N > 130), many of whom have contributed to the tally of \"lab babies.\" At present, 79 lab babies (Cathy, of course, being lab baby 1; there is also 1 lab \"grandchild\"). Together, we are the \"Kovacs Empire.\" Watching the trainees develop into clinicians/scientists/parents and more has been among the greatest joys of my career, and seeing their kids grow up is an added bonus. Of course, other numbers could be thrown into the mix. For example, I have published >300 papers and have been funded by the US National Institutes of Health for >29 consecutive years (along with multiple local, national, other federal funding agencies) and, importantly, have helped launch the careers of many mentees from my lab and elsewhere. The \"Kovacs Babies in the Empire\" email list is broad and gives me an excuse to check in with the group relatively frequently. The other part of my \"legacy,\" of course, is the money I have earned. Sorry to the lab members and readers who expect a cut of this: it all goes to Cathy.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell and spatial transcriptomics define eosinophil heterogeneity during influenza A virus-induced exacerbation of fungal allergic asthma in C57BL/6 mice.","authors":"Anthony J Veltri, Anthony J Wells, Magdaline Baus, Sameer K Mathur, Amali E Samarasinghe","doi":"10.1093/jleuko/qiag120","DOIUrl":"10.1093/jleuko/qiag120","url":null,"abstract":"<p><p>Although eosinophils (EOS) are accepted as transcriptionally heterogeneous in asthma, how allergic inflammation shapes EOS states during influenza A virus (IAV) infection remains undefined. We integrated high-resolution single-cell RNA sequencing, spatial transcriptomics, quantitative immunofluorescence imaging, and cell-cell communication analyses to profile murine lungs across naïve, asthma, influenza (flu), and co-morbid asthma and flu (asthma + flu) conditions. We identified 3 related EOS transcriptional states distributed along a disease-associated continuum. EOS in the flu-only condition preferentially expressed canonical antiviral and interferon-stimulated genes, including Isg15, Gbp2, and Samhd1, whereas asthma + flu EOS had attenuated induction of these programs together with enrichment of genes associated with chemotaxis, adhesion, inflammatory regulation, and metabolic remodeling. Asthma + flu EOS were also enriched for a human asthma-associated high EOS gene signature. A progressive shift in EOS from antigen-presenting programs toward chemotactic and tissue remodeling-associated states, as identified by pseudotime analysis, may imply a changing functional emphasis rather than sustained canonical antiviral activation. Spatial profiling confirmed condition-dependent EOS abundance, increased EOS Alox15 expression in allergic conditions, and disease-specific cellular neighborhoods. Cross-platform analyses identified recurrent predicted interactions between EOS and a distinct Alox15+ alveolar macrophage population. Mast cells adopted infection-specific interleukin-1 and leukocyte-activation transcriptional programs without major compositional changes. Collectively, these findings demonstrate that the type 2 microenvironment reshapes both the transcriptional state and spatial organization of lung EOS during IAV infection, providing an integrated framework for understanding EOS heterogeneity and cellular coordination in the allergic lungs.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding low-density neutrophils in breast and lung cancer: from bystanders to drivers.","authors":"T S C Martins, R Salvador, B F Correia, D Grosa, M Vitorino, I M Sousa, A R Freitas, C Francisco, M Vaz Batista, S Braga, A Jacinto, M G Cabral","doi":"10.1093/jleuko/qiag126","DOIUrl":"10.1093/jleuko/qiag126","url":null,"abstract":"<p><p>Neutrophils, once viewed as short-lived and functionally uniform antimicrobial cells, are now recognized as highly plastic immune regulators with context-dependent roles in cancer. Among circulating neutrophil subsets, low-density neutrophils have emerged as a clinically relevant population in oncology due to their distinct phenotypic, potent immunosuppressive activity, and strong association with disease progression. Low-density neutrophils are rare in healthy individuals but markedly expanded in patients with solid tumors. Low-density neutrophils display enhanced activation, increased expression of immunoregulatory molecules such as programmed death-ligand 1, elevated reactive oxygen species production, and a heightened propensity for neutrophil extracellular trap formation, collectively impairing cytotoxic T cell function and promoting tumor immune evasion. Although low-density neutrophils have been described across multiple malignancies, their biological and clinical relevance has been most characterized in breast and lung cancers. This review synthesizes current knowledge on neutrophil biology, emphasizing the clinical and mechanistic features of low-density neutrophils, with a focus on these 2 tumor types. In breast cancer, increased low-density neutrophil abundance correlates with metastatic disease, poor response to neoadjuvant chemotherapy, immunosuppression, accelerated progression, and reduced survival. In lung cancer, elevated low-density neutrophil frequencies similarly associate with advanced disease stage, unfavorable clinical outcomes, and distinct surface marker profiles distinguishing them from high-density neutrophils. Mechanistic studies indicate that tumor-derived cytokines and chronic inflammation drive low-density neutrophil expansion, functional reprogramming, and tissue trafficking, linking systemic neutrophil dysregulation to advanced disease and metastatic progression. Finally, we highlight emerging biomarkers, unresolved challenges, and therapeutic strategies targeting neutrophil plasticity and low-density neutrophil-mediated immunosuppression, underscoring their potential as actionable components in precision oncology.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hazy mysteries and the major histocompatibility complex: a journey.","authors":"David H Raulet","doi":"10.1093/jleuko/qiag129","DOIUrl":"10.1093/jleuko/qiag129","url":null,"abstract":"<p><p>I was pleased to receive an invitation to write a historical perspective on my career. As I understand it, these perspectives aim to illustrate the often-twisted paths to discoveries, the fortuitous events that often enable them, and the pitfalls along the way. At the same time, they can be expected to illustrate the influence of the particular \"tastes\" and interests of a scientist in the choices that are made along the way and that there are many ways to position oneself in a field of study. This article describes my initial interest in molecular biology, the early events that led me to undertake graduate studies in cellular immunology with a focus on MHC restriction of T cell specificity and T cell activation, and the serendipitous events that led to my eventual transition to a focus on natural killer cells and cancer immunotherapy. I hope that this piece provides some of the illustrations mentioned and will therefore be of interest to a range of readers with an interest in immunology research.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}