Journal of Leukocyte Biology最新文献

{"title":"Diminished FcγRIIa expression reduces antibody-mediated phagocytosis by low-density neutrophils in obesity.","authors":"Carlos Blanco-Camarillo, Nathalia Naranjo-Pinto, Nancy Mora, Aldo Ferreira-Hermosillo, Eileen Uribe-Querol, Carlos Rosales","doi":"10.1093/jleuko/qiag128","DOIUrl":"10.1093/jleuko/qiag128","url":null,"abstract":"<p><p>Obesity is a chronic inflammatory disease associated with an increased risk of various medical complications, including cardiovascular problems, diabetes, and infectious diseases. A central element of the immune system associated with inflammation and antimicrobial function is neutrophils. Recently, distinct neutrophil subpopulations have been described in different conditions. One neutrophil subpopulation, the low-density neutrophils (LDN), is of particular interest because LDN numbers increase significantly in several diseases. However, in the context of obesity, there is little information on the appearance and functions of LDN. Therefore, to evaluate whether LDN numbers increase in individuals with obesity and to explore their functional properties, LDN from individuals with normal weight and from individuals with obesity were isolated, and their phenotypes and microbicidal functions were assessed. In individuals with normal weight, LDN showed enhanced respiratory burst and more efficient antibody-mediated phagocytosis than neutrophils. In individuals with obesity, LDN numbers were elevated. However, in these LDN, phagocytosis and NETosis were impaired. Also, LDN from individuals with obesity had lower expression of the phagocytic receptor FcγRIIa. In addition, although LDN from cancer patients have been reported to be immunosuppressive, LDN either from individuals with normal weight or from individuals with obesity did not inhibit the proliferation of T-cells. Together, these findings suggest that obesity induces elevated numbers of LDN. But, these LDN perform phagocytosis and NETosis less efficiently than LDN from individuals with normal weight. This deficiency could explain, in part, the increased disease severity of infections observed in individuals with obesity.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976888","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":"Tumor-associated neutrophils and macrophages differentially affect T-cell biology in the head and neck cancer tumor microenvironment.","authors":"Xi Wang, Stefan Kasper-Virchow, Hendrik Winkel, Kirsten Bruderek, Michael Pogorzelski, Eric Deuss, Sarah Theurer, Stephan Lang, Cornelius Kürten, Sven Brandau","doi":"10.1093/jleuko/qiag122","DOIUrl":"10.1093/jleuko/qiag122","url":null,"abstract":"<p><p>Intra-tumoral T-cell activity is required for effective antitumor immune responses and is partly regulated by tumor-associated neutrophils and macrophages. Here, we investigated the spatial context of neutrophil/macrophage interactions with CD8+ T cells in head and neck squamous cell carcinoma. Using multiplex immunofluorescence staining of biopsy specimens from 14 patients, we analyzed neutrophils, macrophages, and CD8+ T cells within tumor nests and stromal compartments. All 3 cell types were enriched in the stroma. To characterize spatial immune niches, we defined regions enriched for each cell type and analyzed their overlap. CD8+ T cells showed spatial exclusion from neutrophils, whereas macrophages colocalized with CD8+ T cells. In regions enriched for both neutrophils and CD8+ T cells, neutrophils were associated with reduced CD8+ T-cell proliferation, potentially caused by contact-dependent suppression. These findings demonstrate that neutrophils and macrophages differentially shape CD8+ T-cell distribution and activity within the head and neck cancer microenvironment.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906309","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":"Mitochondrial phosphatase PGAM5 negatively regulates the induction of anti-inflammatory macrophages.","authors":"Young Jun Kang","doi":"10.1093/jleuko/qiag127","DOIUrl":"10.1093/jleuko/qiag127","url":null,"abstract":"<p><p>Macrophage polarization toward anti-inflammatory phenotypes is essential for the resolution of inflammation and restoration of tissue homeostasis, yet the mitochondrial mechanisms governing this process remain poorly defined. This study identifies a novel role for the mitochondrial membrane protein, phosphoglycerate mutase 5 (PGAM5), as a negative regulator of IL-4-driven anti-inflammatory macrophage polarization. PGAM5 selectively controls IL-4-induced phosphorylation of Janus kinase 1 (JAK1), driving the activation of the downstream transcription factor Signal transducer and activator of transcription 6 (STAT6) and thereby regulating anti-inflammatory macrophage polarization. Importantly, PGAM5-dependent regulation of anti-inflammatory responses is independent of dynamin-related protein 1 (DRP1), contrasting with the DRP1-dependent mechanism by which PGAM5 promotes pro-inflammatory macrophage responses. Furthermore, knockdown of PGAM5 markedly potentiated the IL-4-induced expression of the anti-inflammation markers, such as Il10, Tgfb, Arg1, Fizz1, and Ym1, as well as surface expression of CD163 and CD206. At the metabolic level, PGAM5 knockdown facilitated the metabolic reprogramming of macrophages toward enhanced oxidative phosphorylation and fatty acid oxidation, consistent with the bioenergetic demands of anti-inflammatory polarization. Collectively, these findings establish PGAM5 as a central regulator that oppositely controls macrophage polarization, highlighting its potential as a therapeutic target to modulate macrophage-driven inflammation and resolution.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008444","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":"Zinc finger protein 600 is essential for the cytotoxic function of esophageal cancer-associated natural killer cells.","authors":"Jiongming He, Shan Liu, Lingying Wang, Fei Xiong","doi":"10.1093/jleuko/qiag119","DOIUrl":"10.1093/jleuko/qiag119","url":null,"abstract":"<p><p>Natural killer (NK) cells are active tumoricidal cells that inhibit esophageal cancer (EC) development, making them a prospective immunotherapeutic tool. Nonetheless, NK cells undergo both activation and exhaustion in the tumor microenvironment, but the related mechanisms have not been thoroughly understood. Using a chemical-induced EC model, we investigated the expression pattern and functional properties of zinc finger protein 600 (ZNF600) in EC-associated NK cells. For the first time, we revealed that ZNF600 expression was diminished in EC-associated NK cells, particularly those exhibiting the exhaustion phenotype. In vitro silencing of ZNF600 resulted in a remarkable downregulation of tumor necrosis factor, interferon-gamma, and cytolytic perforin and granzyme B, leading to an impairment of NK cell tumoricidal capacity. On the contrary, ZNF600 overexpression promoted NK cell tumoricidal capacity. Adoptive transfer of ZNF600-overexpressing NK cells significantly inhibited the growth of EC implants. Furthermore, EC cells significantly downregulated ZNF600 in NK cells. Interestingly, neutralizing carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) partially restored ZNF600 expression after co-culture with EC cells. Conclusively, the CEACAM1-TIM-3 signaling axis might decrease ZNF600 in EC-associated NK cells and subsequently suppress NK cell-mediated killing of EC cells. This research discovers a novel mechanism by which the EC microenvironment induces NK cell dysfunction.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829420","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":"Dysfunctional neutrophil response in COVID-19 infection varies by subtype.","authors":"Onn Shaun Thein, Kylie B R Belchamber, Jon Hazeldine, Aduragbemi A Faniyi, Frances S Grudzinska, Michael J Hughes, Alice E Jasper, Kay Por Yip, Louise Crowley, Sebastian T Lugg, Elizabeth Sapey, David R Thickett, Aaron Scott, Dhruv Parekh","doi":"10.1093/jleuko/qiag107","DOIUrl":"https://doi.org/10.1093/jleuko/qiag107","url":null,"abstract":"<p><p>The SARS-CoV-2 virus significantly evolved with several new strains identified. Transmissibility has increased with each strain, corresponding with a decrease in mortality. We previously demonstrated novel dysfunctional neutrophil responses in alpha COVID-19 patients compared to community acquired pneumonia controls. We investigated if strain variation altered our previously observed neutrophil dysfunction. Patients with COVID-19 not requiring intensive care were recruited between January 2021 and May 2022 from the Queen Elizabeth Hospital Birmingham; 41 patients with alpha, 32 delta and 14 omicron. Neutrophils isolated from whole blood were investigated for phagocytosis of labelled Streptococcus pneumoniae, transwell migration towards interleukin-8, neutrophil extracellular (NET) formation and surface phenotype. Neutrophil phagocytosis was significantly increased in delta variant (vs alpha p=0.0012, vs omicron p=0.0209). Transwell migration was also significantly reduced in omicron patients (vs alpha p=0.0002, vs delta p=0.0129). There was a significant reduction in NET formation from omicron patients (vs alpha p=0.0031, vs delta p=0.0231). Compared to alpha patients, neutrophils from omicron patients had reduced expression of CD10 (p=0.0004), CD54 (p=0.0015), CD62L (p=0.0013) and CD11c (p<0.0001). CXCR2 expression was higher in neutrophils from omicron compared to alpha patients (p=0.0001). Neutrophil function and phenotype differ between the variants of COVID-19 infection in hospitalised patients. Neutrophil changes suggest more accurate migration in omicron patients, leading to decreased neutrophil host-mediated tissue damage. This may contribute to the overall milder clinical omicron phenotype. Ongoing research and review of therapies remains important alongside viral evolution.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669877","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":"Correction to: Ferroptosis in neutrophils.","authors":"","doi":"10.1093/jleuko/qiag104","DOIUrl":"https://doi.org/10.1093/jleuko/qiag104","url":null,"abstract":"","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"118 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648671","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":"HS1 loss drives cytoskeletal dysregulation and reduces sensitivity to BTK inhibition in chronic lymphocytic leukemia.","authors":"Luca Russo, Marta Sampietro, Marco Cellani, Federica Barbaglio, Francesca Vittoria Sbrana, Giorgio Barigelletti, Jessica Bordini, Dafne Barozzi, Anna Sofia Tascini, Riccardo Campanile, Valeria Cassina, Francesco Mantegazza, Paolo Ghia, Cristina Scielzo","doi":"10.1093/jleuko/qiag099","DOIUrl":"10.1093/jleuko/qiag099","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) is a B cell malignancy driven by aberrant signaling and microenvironmental support. Cytoskeletal remodeling contributes to these mechanisms, where the hematopoietic protein HS1 appears to play a key role. Thus, we generated C57BL/6 HS1 knockout (HS1KO) mice to assess its impact on lymphocyte development. Young HS1KO mice showed some alterations in B cell maturation and T cell differentiation, which appeared to normalize with age. In double-transgenic Eμ-TCL1-HS1KO mice, combining HS1 loss with the standard Eμ-TCL1 CLL mouse model, we observed a trend of reduction in the CD4/CD8 ratio, and disrupted splenic architecture with loss of follicular organization. Transcriptomic and kinase profiling of the human CLL cell line MEC1, in which HS1 was knocked out (MEC1-HS1KO), revealed a coherent impairment in terms of cell mobility as highlighted by severely impaired migration in 2D and 3D environments, reduced chemotactic responses to CXCL12 and CCL19; deregulation of cytoskeletal, adhesion, and apoptotic pathways; and increased resistance to apoptosis. We posited that these defects could reduce sensitivity to BTK (Bruton's tyrosine kinase) inhibition, a standard therapeutic approach in CLL. Primary CLL cells from the spleen of Eμ-TCL1-HS1KO mice appeared to show reduced sensitivity to ibrutinib, a finding that was also observed in adoptive transfer experiments designed to equalize disease burden. Wild-type mice receiving Eμ-TCL1-HS1KO leukemic cells tend to be more resistant to ibrutinib, particularly in the peripheral blood and spleen. All together, these findings establish HS1 as a potential regulator linking B cell receptor signaling, cytoskeletal remodeling, leukemic progression, and response to therapy, supporting its potential as a biomarker for BTK inhibitor sensitivity.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447480","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":"A DLL1-culture system to propagate murine patrolling monocytes from bone marrow progenitors.","authors":"Jessica A F D Silva, Ashina Nagra, Abishek Wadhwa, Samantha Mar, Amelia Tjoa, Stephane Flibotte, Maunish Barvalia, Israel Matos, John Priatel, Danielle L Krebs, Kenneth W Harder","doi":"10.1093/jleuko/qiag103","DOIUrl":"10.1093/jleuko/qiag103","url":null,"abstract":"<p><p>Patrolling monocytes (pMos) scavenge debris from vessel walls and mediate antibody-dependent cellular phagocytosis, making them attractive cell therapy candidates for cancer, atherosclerosis, and Alzheimer's disease. However, methods to generate pMos for cell therapy are not available. To address this, we developed a 2-step procedure to produce pMos in vitro from murine bone marrow (BM). First, myeloid progenitors were expanded and enriched from BM using cytokines for 4 d. Second, expanded progenitors were differentiated into pMos on delta-like ligand 1 (DLL1)-expressing monolayers for 8 d. We confirmed that in vitro grown pMos expressed the transcription factor Nr4a1 (Nur77) and other canonical pMos surface proteins, and depended on Notch signaling for their development. RNA-sequencing revealed that in vitro pMos expressed hallmark pMos genes, including Cx3cr1, Itgax (CD11c), CD43, Fcγr4, and Cd274 (PD-L1), and their gene signatures clustered closely with in vivo blood and BM pMos. Transcriptomic and phenotypic analyses further demonstrated that in vitro pMos were distinct from classical BM macrophages. Phagocytosis assays demonstrated the function of in vitro pMos in cancer cell uptake. Adoptive transfer studies demonstrated that in vitro pMos persisted within the circulation and lung vasculature during the early post-transfer period compared with BM-derived macrophages, consistent with the vascular-patrolling properties of pMos. Adoptive transfer of pMos reduced lung tumor burden in a metastatic model, supporting an anti-tumoral role for pMos and their ability to mediate immune surveillance in vivo. These findings demonstrate that the DLL1 culture system allows for propagation of functional pMos, enabling studies of pMos biology and their therapeutic potential.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562326","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":"Premature birth and Cesarean section are associated with significant differences in neonatal CD4+ T cell gene expression and function.","authors":"Carlos Jesús Ventura-Martínez, Linda Aimara Kempis-Calanis, Sebastian Mijares-Guevara, Alejandra Cedillo-Baños, Ingrid Yaritzit Carreón-Cortés, Darely Gutiérrez-Reyna, Stephania Vázquez-Rodríguez, Addy Cecilia Helguera-Repetto, Claudine Irles, Salvatore Spicuglia, Otoniel Rodríguez-Jorge, María Angélica Santana","doi":"10.1093/jleuko/qiag105","DOIUrl":"10.1093/jleuko/qiag105","url":null,"abstract":"<p><p>Premature birth and cesarean section are associated with increased morbidity and inflammatory diseases. However, their impact on neonatal immunity remains incompletely defined. To explore how gestational age and mode of delivery contribute to early immune programming, we analyzed CD4+ T cells, central regulators of adaptive responses, from preterm neonates and full-term neonates born by cesarean section or vaginal delivery. We performed transcriptomic profiling (mRNA-seq) and functional assessment of T cell activation, proliferation, and cytokine production following stimulation. The mode of delivery emerged as a key factor for CD4+ T cell transcriptome and function. CD4+ T cells from full-term neonates born by vaginal delivery exhibited an immune activation signature, produced higher levels of multiple cytokines, and showed reduced proliferative capacity. In contrast, prematurity was associated with modest changes in basal gene expression relative to full-term cesarean section neonates. CD4+ T cells from preterm neonates displayed enhanced proliferation and increased secretion of inflammatory cytokines (IL-13, TNFα, IL-6, and IL-17F) upon stimulation, consistent with heightened responsiveness. Collectively, our findings show that CD4+ T cells from preterm neonates exhibit augmented inflammatory potential, which becomes more regulated at term. Mode of delivery further contributes to this developmental trajectory: cesarean section is associated with a restrained functional profile, whereas vaginal delivery is associated with a mild immune activation signature and increased responsiveness. These results support a model in which neonatal CD4+ T cell trajectories are established during fetal life and further modulated at birth, highlighting the layered influence of perinatal factors on immune development.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648700","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":"Evaluation of T-cell clonality by T-cell constant β chain (TRBC)1 and TRBC2 expression flow cytometry in hypereosinophilic syndrome.","authors":"Alejandra Sánchez-Santos, Alicia Puente-Fernández, Davinia Godoy-Diaz, Lidia González-Hernández, María Isabel Deniz-Marrero, María Angelina Lemes-Castellano, Carlos Cabrera-López","doi":"10.1093/jleuko/qiag094","DOIUrl":"10.1093/jleuko/qiag094","url":null,"abstract":"<p><p>Hypereosinophilic syndrome is a rare hematopoietic disorder characterized by persistently elevated hypereosinophilia in peripheral blood and tissues, leading to multiorgan damage. Hypereosinophilic syndrome can be classified into different subtypes based on diagnostic criteria and clinical characteristics: primary (neoplastic), secondary (reactive), idiopathic, and familial. Idiopathic is the most common subtype, characterized by systemic symptoms without an identifiable underlying cause. Diagnosis requires the exclusion of all primary and secondary causes of hypereosinophilia. Recently, T-cell receptor constant β chain 1 and T-cell receptor constant β chain 2 have emerged as a powerful tool for assessing T-cell clonality by flow cytometry. We evaluated T-cell receptor constant β chain 1 and T-cell receptor constant β chain 2 expression as a new diagnostic tool for detecting T-cell clonality in hypereosinophilic syndrome. Our findings were consistent with the results of molecular T-cell clonality testing. Flow cytometry is a rapid diagnostic method for assessing T-cell receptor constant β chain restriction and accurately determining the targetable T-cell receptor constant β chain isoform expressed by clonal T-cells in hypereosinophilic syndrome.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430466","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}