Journal of Leukocyte Biology最新文献_第4页

Neutrophils induce effective antibody responses to the pneumococcal conjugate vaccine by inhibiting T regulatory cells. 中性粒细胞通过抑制调节性T细胞诱导对肺炎球菌结合疫苗的有效抗体反应。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-31 DOI: 10.1093/jleuko/qiag112

Essi Y I Tchalla, Anagha Betadpur, Andrew Y Khalil, Elena Lopez, Manmeet Bhalla, Musea Chang, Elizabeth A Wohlfert, Elsa N Bou Ghanem

{"title":"Neutrophils induce effective antibody responses to the pneumococcal conjugate vaccine by inhibiting T regulatory cells.","authors":"Essi Y I Tchalla, Anagha Betadpur, Andrew Y Khalil, Elena Lopez, Manmeet Bhalla, Musea Chang, Elizabeth A Wohlfert, Elsa N Bou Ghanem","doi":"10.1093/jleuko/qiag112","DOIUrl":"10.1093/jleuko/qiag112","url":null,"abstract":"Neutrophils are required for production of protective antibodies in response to the pneumococcal conjugate vaccine (PCV); however, the mechanisms behind that are not known. Using a mouse model, we found that depletion of neutrophils at the time of vaccination in female mice led to aberrant T-cell responses in the spleen, resulting in increased T regulatory cells (Tregs) that was accompanied by a dysregulated cytokine environment. We found that after vaccination, neutrophils influx into secondary lymphoid organs and increase expression of T-cell engaging or inhibiting markers. When we depleted Tregs in neutrophil-deficient mice at the time of vaccination, the opsonic activity of the antibodies and the ability of the sera to protect naïve hosts against pneumococcal infection significantly increased compared with control mice. Importantly, we examined responses after PCV administration in human female participants and found that PCV altered neutrophil phenotype. Additionally, in vitro coculture of donor neutrophils with their peripheral blood mononuclear cells at 1 wk after vaccination resulted in lower percentage and proliferation of FOXP3+ T cells, showing the clinical relevance of this phenotype. This work reveals a new mechanism by which neutrophils ensure protective Ab responses to vaccination by suppressing Tregs.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684890","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}

引用次数: 0

Complement system in bone inflammation and autoimmunity. 骨炎症和自身免疫中的补体系统。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-31 DOI: 10.1093/jleuko/qiag109

Adrita Guha, Praneet Wahi, Girdhari Lal

引用次数: 0

The pentose phosphate pathway in immunotherapy. 免疫治疗中的戊糖磷酸途径。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-31 DOI: 10.1093/jleuko/qiag106

Rachel D Loo, John Blazeck

引用次数: 0

Obesity hampers bacteria killing by human neutrophils. 肥胖阻碍了人体中性粒细胞杀死细菌。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-31 DOI: 10.1093/jleuko/qiag111

Nathalia Naranjo-Pinto, Carlos Blanco-Camarillo, Nancy Mora, Sergio Quintero-Ardila, Aldo Ferreira-Hermosillo, Eileen Uribe-Querol, Carlos Rosales

{"title":"Obesity hampers bacteria killing by human neutrophils.","authors":"Nathalia Naranjo-Pinto, Carlos Blanco-Camarillo, Nancy Mora, Sergio Quintero-Ardila, Aldo Ferreira-Hermosillo, Eileen Uribe-Querol, Carlos Rosales","doi":"10.1093/jleuko/qiag111","DOIUrl":"10.1093/jleuko/qiag111","url":null,"abstract":"Obesity is a disease associated with an increased risk of various medical complications, including cardiovascular problems, diabetes, and infectious diseases. The higher incidence of infections in individuals with obesity is likely due to impaired immune functions. Neutrophils deploy microbicidal functions. However, it is unclear whether neutrophils in individuals with obesity function effectively against infections. To evaluate whether neutrophils in obesity have dysfunctional antimicrobial functions, neutrophils from individuals with normal weight and from individuals with obesity were isolated, and their phenotype and microbicidal functions were assessed. Neutrophils from individuals with obesity had higher expression of CD66b, CD11b, CD15, CD14, CD18, and CD182 on their membranes. The higher expression of these molecules correlated with higher body mass index, suggesting that obesity is associated with neutrophil activation. Accordingly, the phorbol 12-myristate 13-acetate (PMA)-induced respiratory burst in neutrophils from individuals with obesity was greater than in those from individuals without obesity, whereas phagocytosis and PMA-induced NETosis were comparable between neutrophils from individuals with or without obesity, implying that neutrophil functions are not impaired by obesity. However, neutrophil extracellular trap formation of neutrophils from individuals with obesity was selectively reduced in response to Staphylococcus aureus. Nevertheless, the actual killing of these bacteria was similar between neutrophils from individuals with or without obesity. In contrast, neutrophils from individuals with obesity exhibited impaired killing of Pseudomonas aeruginosa and of Klebsiella quasipneumoniae. Together, these findings suggest obesity induces neutrophil activation but disrupts pathogen-specific antimicrobial mechanisms of neutrophils. This deficiency in pathogen clearance could explain the increased susceptibility to infections observed in individuals with obesity.","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":"148684895","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}

引用次数: 0

TLR-mediated calcium signaling regulates killing capacity of expanded NK cells: challenges for potential AML immunotherapy. tlr介导的钙信号调节扩增NK细胞的杀伤能力：潜在AML免疫治疗的挑战。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag092

Vojtěch Graman, Adéla Jílková, Marek Jedlička, Veronika Švubová, Zuzana Tomášiková, Matúš Otruba, Kateřina Kuglerová, Eva Mašínová, Jana Szabová, Michal Santocki, Tereza Fiedlerová, Marcela Hortová Kohoutková, Jan Frič

{"title":"TLR-mediated calcium signaling regulates killing capacity of expanded NK cells: challenges for potential AML immunotherapy.","authors":"Vojtěch Graman, Adéla Jílková, Marek Jedlička, Veronika Švubová, Zuzana Tomášiková, Matúš Otruba, Kateřina Kuglerová, Eva Mašínová, Jana Szabová, Michal Santocki, Tereza Fiedlerová, Marcela Hortová Kohoutková, Jan Frič","doi":"10.1093/jleuko/qiag092","DOIUrl":"10.1093/jleuko/qiag092","url":null,"abstract":"Natural killer (NK) cells are central to cancer immunosurveillance and immunotherapy. Their ability to engage in killing is critical for efficient target elimination and depends on tightly regulated Ca2+ signaling controlling granzyme degranulation. Toll-like receptor (TLR) engagement has been linked to Ca2+ signaling in other immune cell types, while a specific role in NK cells remains unresolved. Given that NK cells express a broad range of TLRs, and that presence of TLR ligands-including damage- and pathogen-associated molecular patterns-can influence clinical scenarios including adoptive NK cell therapy, investigating TLR-driven Ca2+ signaling in NK cells is particularly relevant. Here, we examined how stimulation with selected TLR ligands influences Ca2+ signaling and NK cell activity. Immediate stimulation induced a rapid elevation of cytosolic Ca2+ in expanded NK cells. Functionally, TLR stimulation increased degranulation and enhanced cytotoxicity at high effector-to-target ratios. Under conditions of target excess, however, TLR-treated NK cells displayed impaired killing, likely due to unbalanced Ca2+ levels. These findings demonstrate that TLR signaling directly modulates Ca2+ flux in NK cells and can either potentiate or impair cytotoxic activity depending on context. Although clinical implications remain hypothetical, such TLR-driven dysregulation affects NK cell killing activity in the inflammatory or pathogen-rich environments frequently encountered after chemotherapy. Our findings suggest that TLR-Ca2+ impact on cytotoxicity should be considered in adoptive transfer therapies where previous treatment affects systemic levels of TLR ligands, such as in patients with acute myeloid leukemia, where NK cell immunotherapy is frequently tested in trials.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578946","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}

引用次数: 0

Sialylation modulates basophil responsiveness to galectin-3-dependent activation. 唾液酰化调节嗜碱性粒细胞对半乳糖凝集素-3依赖性激活的反应性。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag087

Laurent Ehrlich, Donald W MacGlashan, Robert Anthony, Michelle Conroy, Anja P Bieneman, John T Schroeder

{"title":"Sialylation modulates basophil responsiveness to galectin-3-dependent activation.","authors":"Laurent Ehrlich, Donald W MacGlashan, Robert Anthony, Michelle Conroy, Anja P Bieneman, John T Schroeder","doi":"10.1093/jleuko/qiag087","DOIUrl":"10.1093/jleuko/qiag087","url":null,"abstract":"Basophils secrete histamine and IL-4/13 when cocultured with human lung adenocarcinoma cells (A549 cells). Previous studies have revealed that this interaction is dependent on galectin-3 expression on the surface of A549 cells (EC-Gal-3), IgE present on the surface of IL-3 primed basophils, and direct physical interaction between the two cell types, indicating a cognate interaction between IgE and Gal-3. Reciprocal secretion of protumorigenic cytokines (IL-6/VEGF-A) from A549 cells also results. Here, we further define the biological parameters required for this mode of activation. EC-Gal-3 stimulus has ∼20-fold less IgE crosslinking capacity compared with standard anti-IgE. The capacity of IgE-bearing basophils to elicit an EC-Gal-3-mediated response correlates with their responsiveness to standard anti-IgE stimulation, which is known to vary widely among individuals. However, unlike standard anti-IgE stimulation, basophil releasability in response to EC-Gal-3 is influenced by glycosylation patterns on surface-bound IgE. Specifically, bulk sialylation on IgE molecules suppress cellular releasability. Whole-cell basophil sialylation also suppresses EC-Gal-3 mediated activation. Gal-3 is an endogenous lectin with multivalent binding capacity and is implicated in a range of diseases involving immune modulation, organ fibrosis, and tumor metastasis. These results can help identify specific physiological and pathophysiological conditions by which IgE:Gal-3 interactions drive disease processes including wound healing, cancer, and fibrosis, including that which occurs in asthma.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13390634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148329809","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}

引用次数: 0

A role for noncoding RNAs and alternative splicing in the regulation of neutrophil activation and gene expression in systemic lupus erythematosus. 非编码rna和选择性剪接在系统性红斑狼疮中性粒细胞活化和基因表达调控中的作用。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag100

Grace Filbertine, Alzbeta Chabronova, Xuan Liu, Sam Haldenby, Huw Batten Thomas, Zoe McLaren, Mandy Jayne Peffers, Helen Louise Wright

{"title":"A role for noncoding RNAs and alternative splicing in the regulation of neutrophil activation and gene expression in systemic lupus erythematosus.","authors":"Grace Filbertine, Alzbeta Chabronova, Xuan Liu, Sam Haldenby, Huw Batten Thomas, Zoe McLaren, Mandy Jayne Peffers, Helen Louise Wright","doi":"10.1093/jleuko/qiag100","DOIUrl":"10.1093/jleuko/qiag100","url":null,"abstract":"Excess neutrophil apoptosis and the release of neutrophil extracellular traps (NETs) in systemic lupus erythematosus (SLE) lead to the accumulation of cell debris and the production of auto-antibodies targeting nuclear proteins and DNA. SLE neutrophil activation is regulated by changes in gene expression, notably expression of type I interferon-response genes and genes coding for granule proteins. This observational study measured both mRNA and small noncoding RNAs in SLE (n = 11) and healthy control (HC, n = 10) ultra-pure blood neutrophils to identify changes in expression that are involved in regulating neutrophil phenotype. Using RNAseq, we identified significant differential expression (DE) of 69 microRNAs, 63 other small noncoding RNAs, 236 piwiRNAs, and 83 tRNA fragments in SLE neutrophils compared to HC (false discovery rate [FDR] adj. P < 0.05). We also identified 78 significant alternative splicing events across 64 genes (FDR adj. P < 0.05, Δpercent spliced in (PSI) > 0.1 or < -0.1). Bioinformatic analysis of miRNA:mRNA DE genes predicted significant activation of autophagy, neutrophil degranulation, interferon alpha/beta signaling, and apoptosis pathways in SLE neutrophils. Translation and mRNA processing were predicted to be downregulated. microRNAs implicated in NETs production were miR-155-5p, miR-146a-5p, and miR-let-7b-5p (FDR adj. P < 0.05). SNORD89 was identified as a potential promoter of apoptosis in SLE neutrophils, along with alternative splicing of apoptosis genes myeloid cell leukemia-1 (MCL1), caspase-8 (CASP8), and death-associated protein kinase-2 (DAPK2) (FDR adj. P < 0.05). Our study, for the first time, describes dysregulated expression of small noncoding RNAs in SLE neutrophils and proposes noncoding RNA and alternative gene splicing as regulators of neutrophil-driven disease pathology in SLE.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471144","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}

引用次数: 0

An optimized method to differentiate HL60 cells into neutrophil-like cells. HL60细胞向中性粒细胞样细胞分化的优化方法。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag081

Samuel P Collie, Grant Yu, Suraj S Rawat, Catharina Rypstra, Carole A Parent

引用次数: 0

High CD163+CD206+ macrophage infiltration in the bone marrow microenvironment of newly diagnosed multiple myeloma patients. 新发多发性骨髓瘤患者骨髓微环境中CD163+CD206+巨噬细胞的高浸润

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag076

Dong-Hai Han, Ya-Ru Li, Hui-Ping Li, Xiao-Qin Pian, Jin-Hong Gao, Ya-Peng Zhang, Bin-Tao Huang, Da Gao, Hong-Yan Zhao

{"title":"High CD163+CD206+ macrophage infiltration in the bone marrow microenvironment of newly diagnosed multiple myeloma patients.","authors":"Dong-Hai Han, Ya-Ru Li, Hui-Ping Li, Xiao-Qin Pian, Jin-Hong Gao, Ya-Peng Zhang, Bin-Tao Huang, Da Gao, Hong-Yan Zhao","doi":"10.1093/jleuko/qiag076","DOIUrl":"10.1093/jleuko/qiag076","url":null,"abstract":"Multiple myeloma (MM) is a neoplastic disease caused by abnormal clonal plasma cells in the bone marrow (BM). Macrophages (MФs) are essential components of BM microenvironment and crucial mediators of plasma cells. Therefore, investigating alterations in the specific MФ subsets within the MM BM microenvironment is of significant importance for elucidating the underlying mechanisms of MM. Here, using flow cytometry, we characterized the dynamics of BM MФ subsets in newly diagnosed multiple myeloma (NDMM) patients and complete remission multiple myeloma (CRMM) patients. We found that NDMM patients exhibited increased infiltration of CD163+CD206+ MФs and elevated levels of interleukin (IL)-6 and IL-10 in the BM compared with CRMM patients and healthy control subjects. BM intermediate monocytes and nonclassical monocytes were increased in NDMM patients compared with those in CRMM patients and healthy control subjects. Furthermore, we observed upregulated CCR2 and CSF-R expression on the BM CD163+CD206+ MФs. Notably, the BM CD163+CD206+CCR2+ MФs were positively correlated with the increased level of IL-6, while CD163+CD206+CSF-R+ MФs were positively correlated with the level of IL-10. Additionally, clinical correlation analysis revealed that an increased proportion of CD163+CD206+CCR2+ MФs was negatively correlated with hemoglobin levels and positively correlated with β2-microglobulin and lactate dehydrogenase. Moreover, a higher proportion of CD163+CD206+CCR2+ MФs was detected in the BM of MM patients with poor prognosis. Altogether, our findings suggest that higher proportion of BM CD163+CD206+ MФs is involved in pathogenesis of MM, and that CCR2 may be potential therapeutic targets for improving antitumor therapy in MM.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308148","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}

引用次数: 0

Sombrero vesicles: from overlooked structures to primary mediators of eosinophil secretion. 草帽囊泡：从被忽视的结构到嗜酸性粒细胞分泌的主要介质。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag072

Rossana C N Melo, Peter F Weller

{"title":"Sombrero vesicles: from overlooked structures to primary mediators of eosinophil secretion.","authors":"Rossana C N Melo, Peter F Weller","doi":"10.1093/jleuko/qiag072","DOIUrl":"10.1093/jleuko/qiag072","url":null,"abstract":"Eosinophils, cells of the innate immune system, have a unique architecture, which includes morphologically complex secretory granules and a prominent, activation-responsive vesiculotubular system. In human eosinophils, this system is collectively termed eosinophil sombrero vesicles (EoSVs) because of its peculiar morphology feasibly identifiable by transmission electron microscopy. Considered as \"microgranules\" or \"small granules\" in the past, EoSVs are currently defined as active components of the eosinophil secretory pathway, sprouting from specific granules and trafficking granule-derived products in the eosinophil cytoplasm. Eosinophil secretory proteins associated with EoSVs include cationic proteins, cytokines, cytokine receptors, membrane fusion complexes, and tetraspanins. Beyond the intracellular landscape, emerging evidence has revealed a more complex functional repertoire for EoSVs. This review offers an overview of EoSVs as key participants in the mechanisms of eosinophil secretion during immune responses, incorporating the recent understanding of these transport carriers as extracellular vesicles, potentially implicated in the traffic of eosinophil products in the extracellular medium and intercellular communication.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175781","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}

引用次数: 0