Journal of Leukocyte Biology最新文献

{"title":"Unraveling spontaneous humoral immune responses against human cancer: a road to novel immunotherapies.","authors":"Jose R Conejo-Garcia, Luis U Lopez-Bailon, Carmen M Anadon","doi":"10.1093/jleuko/qiae179","DOIUrl":"10.1093/jleuko/qiae179","url":null,"abstract":"<p><p>In immuno-oncology, the focus has traditionally been on αβ T cells, and immune checkpoint inhibitors that primarily target PD-1 or CTLA4 in these lymphocytes have revolutionized the management of multiple human malignancies. However, recent research highlights the crucial role of B cells and the antibodies they produce in antagonizing malignant progression, offering new avenues for immunotherapy. Our group has demonstrated that dimeric Immunoglobulin A can penetrate tumor cells, neutralize oncogenic drivers in endosomes, and expel them from the cytosol. This mechanistic insight suggests that engineered antibodies targeting this pathway may effectively reach previously inaccessible targets. Investigating antibody production within intratumoral germinal centers and understanding the impact of different immunoglobulins on malignant progression could furnish new tools for the therapeutic arsenal, including the development of tumor-penetrating antibodies. This review aims to elucidate the nature of humoral adaptive immune responses in human cancer and explore how they could herald a new era of immunotherapeutic modalities. By expanding the scope of antitumor immunotherapies, these approaches have the potential to benefit a broader range of cancer patients, particularly through the utilization of tumor cell-penetrating antibodies.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"919-926"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080539","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: IRG1/ACOD1 promotes neutrophil reverse migration and alleviates local inflammation.","authors":"","doi":"10.1093/jleuko/qiae194","DOIUrl":"10.1093/jleuko/qiae194","url":null,"abstract":"","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1215"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125976","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":"scRNA-seq profiling of human granulocytes reveals expansion of developmentally flexible neutrophil precursors with mixed neutrophil and eosinophil properties in asthma.","authors":"Nana-Fatima Haruna, Yuliya Politanska, Andrew R Connelly, Kathrine O'Connor, Sourav Bhattacharya, Grace E Miklaszewski, Xóchitl G Pérez-Leonor, Geddy Rerko, Ian T Hentenaar, Doan C Nguyen, Pedro Alberto Lamothe Molina, Bruce S Bochner, Hiam Abdala-Valencia, Michelle A Gill, F Eun-Hyung Lee, Sergejs Berdnikovs","doi":"10.1093/jleuko/qiae120","DOIUrl":"10.1093/jleuko/qiae120","url":null,"abstract":"<p><p>Neutrophils and eosinophils share common hematopoietic precursors and usually diverge into distinct lineages with unique markers before being released from their hematopoietic site, which is the bone marrow (BM). However, previous studies identified an immature Ly6g(+) Il-5Rα(+) neutrophil population in mouse BM, expressing both neutrophil and eosinophil markers suggesting hematopoietic flexibility. Moreover, others have reported neutrophil populations expressing eosinophil-specific cell surface markers in tissues and altered disease states, confusing the field regarding eosinophil origins, function, and classification. Despite these reports, it is still unclear whether hematopoietic flexibility exists in human granulocytes. To answer this, we utilized single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing to profile human BM and circulating neutrophils and eosinophils at different stages of differentiation and determine whether neutrophil plasticity plays role in asthmatic inflammation. We show that immature metamyelocyte neutrophils in humans expand during severe asthmatic inflammation and express both neutrophil and eosinophil markers. We also show an increase in trilobed eosinophils with mixed neutrophil and eosinophil markers in allergic asthma and that interleukin-5 promotes differentiation of immature blood neutrophils into trilobed eosinophilic phenotypes, suggesting a mechanism of emergency granulopoiesis to promote myeloid inflammatory or remodeling response in patients with chronic asthma. By providing insights into unexpectedly flexible granulocyte biology and demonstrating emergency hematopoiesis in asthma, our results highlight the importance of granulocyte plasticity in eosinophil development and allergic diseases.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1184-1197"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175668","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 enigmatic AHRR: beyond aryl hydrocarbon receptor repression.","authors":"Mark E Hahn, David H Sherr","doi":"10.1093/jleuko/qiae163","DOIUrl":"10.1093/jleuko/qiae163","url":null,"abstract":"","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"915-918"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727221","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":"Comprehensive mapping of immune perturbations associated with secondary hemophagocytic lymphohistiocytosis.","authors":"Yinchun Chen, Haimei Deng, Ruiqing Zhou, Xiaotao Jiang, Huijuan Wang, Songqing Xin, Wenjian Mo, Shunqing Wang, Yufeng Liu","doi":"10.1093/jleuko/qiae138","DOIUrl":"10.1093/jleuko/qiae138","url":null,"abstract":"<p><p>Secondary hemophagocytic lymphohistiocytosis (sHLH) is a hyperinflammatory syndrome characterized by immune disorders. It is imperative to elucidate the immunophenotypic panorama and the interactions among these cells in patients. Human peripheral blood mononuclear cells were collected from healthy donors and sHLH patients and tested using multicolor flow cytometry. We used FlowSOM to explore and visualize the immunophenotypic characteristics of sHLH. By demonstrating the phenotypes of immune cells, we discovered that sHLH patients had significantly higher levels of CD56+ monocytes, higher levels of myeloid-derived suppressor cells, low-density neutrophil-to-T cell ratio, and higher heterogeneous T cell activation than healthy donors. However, natural killer cell cytotoxicity and function were impaired. We then assessed the correlations among 30 immune cell types and evaluated metabolic analysis. Our findings demonstrated polymorphonuclear myeloid-derived suppressor cells, CD56+ monocytes, and neutrophil-to-T cell ratio were elevated abnormally in sHLH patients, which may indicate an association with immune overactivation and inflammatory response. We are expected to confirm that they are involved in the occurrence of the disease through further in-depth research.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1109-1126"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554966","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":"Eosinophil specialization is regulated by exposure to the esophageal epithelial microenvironment.","authors":"Julia L M Dunn, Andrea Szep, Emily Gonzalez Galan, Simin Zhang, Justin Marlman, Julie M Caldwell, Ty D Troutman, Marc E Rothenberg","doi":"10.1093/jleuko/qiae102","DOIUrl":"10.1093/jleuko/qiae102","url":null,"abstract":"<p><p>Distinct subsets of eosinophils are reported in inflammatory and healthy tissues, yet the functions of uniquely specialized eosinophils and the signals that elicit them, particularly in eosinophilic esophagitis, are not well understood. Herein, we report an ex vivo system wherein freshly isolated human eosinophils were cocultured with esophageal epithelial cells and disease-relevant proinflammatory (IL-13) or profibrotic (TGF-β) cytokines. Compared with untreated cocultures, IL-13 increased expression of CD69 on eosinophils, whereas TGF-β increased expression of CD81, CD62L, and CD25. Eosinophils from IL-13-treated cocultures demonstrated increased secretion of GRO-α, IL-8, and macrophage colony-stimulating factor and also generated increased extracellular peroxidase activity following activation. Eosinophils from TGF-β-treated cocultures secreted increased IL-6 and exhibited increased chemotactic response to CCL11 compared with eosinophils from untreated or IL-13-treated coculture conditions. When eosinophils from TGF-β-treated cocultures were cultured with fibroblasts, they upregulated SERPINE1 expression and fibronectin secretion by fibroblasts compared with eosinophils that were cultured with granulocyte macrophage colony-stimulating factor alone. Translational studies revealed that CD62L was heterogeneously expressed by eosinophils in patient biopsy specimens. Our results demonstrate that disease-relevant proinflammatory and profibrotic signals present in the esophagus of patients with eosinophilic esophagitis cause distinct profiles of eosinophil activation and gene expression.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1007-1020"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898053","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":"Alternative activation of mast cells by CD4+ T helper cells.","authors":"Edouard Leveque, Louise Battut, Camille Petitfils, Salvatore Valitutti, Nicolas Cenac, Gilles Dietrich, Eric Espinosa","doi":"10.1093/jleuko/qiae139","DOIUrl":"10.1093/jleuko/qiae139","url":null,"abstract":"<p><p>Effector CD4+ T (Teff) lymphocytes infiltrate sites of inflammation and orchestrate the immune response by instructing local leukocytes. Mast cells (MCs) are tissue sentinel cells strategically located near blood vessels and T cell-rich areas. MC/Teff cell interactions shape Teff cell responses, but in turn, Teff cell action on MCs is still poorly understood. Here, we analyzed the human MC/Teff cell interplay through both the application of RNA sequencing and functional assays. We showed that activated Teff cells induce a specific transcriptomic program in MCs including production of both inflammatory cytokines and chemokines, prostaglandin, and a FcεRI-dependent degranulation facilitation, thereby driving them toward an inflammatory phenotype. Moreover, Teff cells induce in MCs the capacity to interact with CD4+ T cells through a wide range of dedicated soluble and membrane ligands and to play the role of antigen-presenting cells.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1127-1141"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446378","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":"Modeling of host PDZ-dependent interactions with SARS-CoV-2 envelope protein and changes in PDZ protein expression in macrophages and dendritic cells.","authors":"Jorge Rosas-García, Alberta Jaqueline Padilla-Zúñiga, Antonia Ávila-Flores, Luis Horacio Gutiérrez-González, Isabel Mérida, Teresa Santos-Mendoza","doi":"10.1093/jleuko/qiae118","DOIUrl":"10.1093/jleuko/qiae118","url":null,"abstract":"<p><p>PDZ (PSD-95 [postsynaptic density protein 95]/Dlg [Discs large]/ZO-1 [zonula occludens-1]) domain-containing proteins constitute a large family of scaffolds involved in a wide range of cellular tasks and are mainly studied in polarity functions. Diverse host PDZ proteins can be targeted by viral pathogens that express proteins containing PDZ-binding motifs (PDZbms). Previously, we have identified host PDZ-based interactions with the SARS-CoV-2 E protein (2E) in human monocytes. Here, we deepen the study of these interactions by docking and molecular dynamics analyses to identify the most favorable PDZ-PDZbm interaction of 7 host PDZ proteins with the PDZbm of 2E. In addition, we analyzed changes in the expression of 3 of the PDZ proteins identified as 2E interactors in monocytes (syntenin, ZO-2, and interleukin-16), in human monocyte-derived macrophages and in dendritic cells upon stimulation. Our results suggest that these PDZ proteins may have important functions in professional antigen-presenting cells, and their targeting by the PDZbm of 2E, a central virulence determinant of SARS-CoV-2, supports the hypothesis that such PDZ-dependent interaction in immune cells may constitute a viral evasion mechanism. An inhibitor design based on the PDZbm of 2E in the development of drugs against a variety of diseases is discussed.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"995-1006"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945198","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":"Upregulation of granzyme B and C-X3-C motif receptor 1 in circulating plasmablasts was negatively regulated by Notch signal in patients with systemic lupus erythematosus.","authors":"Zhonghui Zhang, Zihang Yuan, Yiying Wang, Ya-Hui Zhang, Qi Li, Xingyue Zeng, Zhao Guan, Ayibaota Bahabayi, Pingzhang Wang, Chen Liu","doi":"10.1093/jleuko/qiae127","DOIUrl":"10.1093/jleuko/qiae127","url":null,"abstract":"<p><p>As one molecule related to cytotoxicity, surface expression of C-X3-C motif receptor 1 (CX3CR1) was highly correlated with intracellular granzyme B (GZMB) in natural killer and cytolytic T cells. However, the expression of CX3CR1 and GZMB in B cells has not been clarified, and their clinical significance in systemic lupus erythematosus (SLE) remains unclear. This study aimed to clarify the changes and clinical significance of peripheral blood B cells expressing GZMB and/or CX3CR1 in SLE. Peripheral blood was collected from 39 patients with SLE and 48 healthy controls. We found that GZMB and CX3CR1 expression varied in different B-cell subsets, with plasmablasts possessing the highest positive percentages, consistent with bioinformatics prediction. GZMB+ and CX3CR1+ percentages in circulating B cells and plasmablasts were increased in patients with SLE. CX3CR1 was upregulated on B cells after in vitro stimulation. Notch intracellular domain expression was significantly decreased in plasmablasts of patients with SLE, and CX3CR1 in plasmablasts was downregulated with the addition of JAG1. In conclusion, GZMB and CX3CR1 were increased in B cells and in plasmablasts of patients with SLE and CX3CR1 was negatively regulated by Notch signal in plasmablasts, which may be involved in SLE pathogenesis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1061-1071"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247138","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":"Crosstalk between circBMI1 and miR-338-5p/ID4 inhibits acute myeloid leukemia progression.","authors":"Xiaoyu Su, Biwen Hu, Jing Yi, Qian Zhao, Yongqing Zhou, Xin Zhu, Delong Wu, Yaohua Fan, Jiang Lin, Chenxi Cao, Zhaoqun Deng","doi":"10.1093/jleuko/qiae136","DOIUrl":"10.1093/jleuko/qiae136","url":null,"abstract":"<p><p>BMI1 polycomb ring finger proto-oncogene (BMI1) is involved in the pathogenesis of different cancers, including acute myeloid leukemia (AML). However, the role of the circular RNA of BMI1 (circBMI1) has not been studied. Our study aimed to investigate the role and mechanism of circBMI1 in AML. circBMI1 was significantly decreased in bone marrow mononuclear cells aspirated from patients with AML. Receiver operating characteristic curve analysis showed that circBMI1 could distinguish patients with AML from controls. By overexpressing and knocking down circBMI1 in HL-60 cells, we found that circBMI1 inhibited cell proliferation, promoted apoptosis, and increased chemotherapeutic drug sensitivity in AML. Experiments using severe combined immune-deficient mice and circBMI1 transgenic mice showed that mice with circBMI1 overexpression had lower white blood cell counts, which suggested less severe AML invasion. RNA immunoprecipitation and dual-luciferase reporter assay revealed binding sites among circBMI1, miR-338-5p, and inhibitor of DNA-binding protein 4 (ID4). Rescue experiments proved that circBMI1 inhibited AML progression by binding to miR-338-5p, which affected the expression of ID4. By coculturing exosomes extracted from circBMI1-HL-60 and small interfering circBMI1-HL-60 cells with HL-60 cells, we found that exosomes from circBMI1-HL-60 cells showed tumor-suppressive effects, namely inhibiting HL-60 proliferation, promoting apoptosis, and increasing chemotherapeutic drug sensitivity. Exosomes from small interfering circBMI1-HL-60 cells showed the opposite effects. circBMI1 may act as an exosome-dependent tumor inhibitor. circBMI1, a potential biomarker for clinical diagnosis, acts as a tumor suppressor in AML by regulating miR-338-5p/ID4 and might affect the pathogenesis of AML by exosome secretion.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1080-1093"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306142","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}