Journal of Leukocyte Biology最新文献

{"title":"AML1-ETO and CCND2 overexpression- cooperate to drive acute myeloid leukemia initiation and progression.","authors":"Junli Mou, Qianqian Huang, Xiaoyu Liu, Wenbing Liu, Yu Liu, Yihan Mei, Runxia Gu, Yingxi Xu, Kejing Tang, Zheng Tian, Haiyan Xing, Qing Rao, Min Wang, Shaowei Qiu, Jianxiang Wang","doi":"10.1093/jleuko/qiaf072","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf072","url":null,"abstract":"<p><p>Increasing numbers of clinical cohorts have detected CCND2 mutations in acute myeloid leukemia (AML), especially in the subtype of AML with t(8;21) translocation. As known, this AML subtype is characterized by the formation of AML1-ETO fusion gene. However, AML1-ETO fusion gene alone is not sufficient to drive leukemia development, additional mutations are required for leukemogenesis. In this study, we aim to investigate whether mutated CCND2 can cooperate with AML1-ETO fusion gene to drive leukemia initiation and progression. In our previous study, the conditional AML1-ETO knock-in mouse model (AML1/ETO mouse), which represented a pre-leukemia stage as myeloproliferative neoplasm phenotype, was established. To confirm whether the AML1-ETO and CCND2 mutation can cooperate to drive leukemia, the mice transduction and transplantation model harboring both AML1-ETO and CCND2 gene (both wildtype and mutant) were established. Upon the assessment of the phenotype, biological features and survival of the mice, only the mice overexpressing the AML1-ETO and CCND2 simultaneously were eventually progressed to leukemia. Besides, compared to mice overexpressing AML-ETO gene alone, mTOR and cell cycle-related pathways were significantly enriched in mice harboring both AML1-ETO and CCND2. And the selective mTOR inhibitor, Everolimus, can reduce the leukemia burden and prolong the survival of this group of mice. In conclusion, it was confirmed that introduction of the CCND2 gene into the AML/ETO pre-leukemia mice could trigger the development of leukemia. It was also confirmed that CCND2 overexpression resulted in the upregulation of the mTOR pathway and inhibiting the pathway might be a therapeutic strategy for this subtype of leukemia.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119623","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 influence of skin microbial ecology on γδ T-cell immune pathways in allergic dermatitis models in mice.","authors":"Zonghao You, Xiaoyan Zhang, Sujie Huang, Denghui Chen, Yifan Zhu, Gen Li, Xi Chen","doi":"10.1093/jleuko/qiae244","DOIUrl":"10.1093/jleuko/qiae244","url":null,"abstract":"<p><p>Atopic dermatitis is a complex disease influenced by alterations in the skin microbiome and immune dysregulation. Despite the recognized role of these factors, the specific pathways by which distinct microbial populations affect skin immunity remain insufficiently understood. On a molecular level, the pathogenesis of atopic dermatitis involves critical cytokines such as IL-4, IL-17, interferon-γ, and IL-10, which contribute to the imbalance in T helper cell responses. Importantly, gamma-delta (γδ) T cells, which produce these cytokines and infiltrate affected epithelial cells in atopic dermatitis, have been underexplored. This study seeks to alleviate atopic dermatitis symptoms in mice by adjusting both peripheral and local immune environments through the transplantation of skin microbiota. By employing 16S rRNA sequencing, we characterized the skin microbiome of the mouse model. Our results demonstrate that microbiota intervention significantly reduces skin thickening and serum IgE levels in DNCB-induced atopic dermatitis mice. Additionally, changes in skin microbiota modulated immune cell dynamics, restoring the T helper 1 / T helper 2 balance and leading to clinical improvement. These findings highlight the critical role of skin microbiota in shaping immune responses, positioning microbiota-based therapies as a potential treatment for atopic dermatitis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581401","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":"No-lyse no-wash flow cytometry method for ex vivo study of human neutrophils.","authors":"Yun-Shan Tsai, Iwona Niemietz, Martina Sundqvist, Kelly L Brown","doi":"10.1093/jleuko/qiaf050","DOIUrl":"10.1093/jleuko/qiaf050","url":null,"abstract":"<p><p>Neutrophils are vital immune cells involved in immunity via their effector roles and death. While their rapid response to the environment is crucial for immune function, it also makes them difficult to study. Here, we provide a no-lyse no-wash (NLNW) flow cytometry protocol to quantify neutrophil viability and death in whole blood with minimal sample handling. Viability of neutrophils was measured by Annexin V/7AAD staining in whole blood at 0 and 20 h. Associated cost, sample volume, and neutrophil survival were compared with traditional density-gradient isolated neutrophils. The NLNW analysis of whole blood immediately after collection showed ∼85% viable neutrophils. After 20 h of incubation, viability dropped to ∼70%, yet was significantly greater compared with isolated neutrophils, where half the population (∼44%) entered early-stage apoptosis. The NLNW flow cytometry method is an efficient and cost-effective method to measure neutrophil viability in small volumes of whole blood with minimal sample handling.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022346","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":"CD300ld promotes neutrophil bacterial phagocytosis in sepsis.","authors":"Yuichi Akama, Atsushi Murao, Monowar Aziz, Ping Wang","doi":"10.1093/jleuko/qiaf063","DOIUrl":"10.1093/jleuko/qiaf063","url":null,"abstract":"<p><p>Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. Neutrophils act as first line of defense against infection, but their function can become impaired in sepsis. CD300 antigen-like family member d (CD300ld), predominantly expressed on neutrophils, associates with Fc receptor common gamma-chain (FcRγ chain), a component vital for phagocytosis. In this study, we investigated the role of CD300ld in neutrophil phagocytosis. Our results demonstrate a marked decrease in CD300ld expression on neutrophils isolated from both septic mice and patients. CD300ld was positively correlated with bacterial phagocytosis in neutrophils. The transcriptomic analysis of CD300ld knock-out neutrophils revealed a downregulation of genes related to defense response to bacteria, suggesting that CD300ld is a key modulator of bacterial clearance. Stimulation of CD300ld with an agonist antibody in neutrophils led to the activation of Rac2, a key regulator of actin polymerization, facilitating the enhanced phagocytosis. Furthermore, CD300ld activation significantly enhanced the in vitro phagocytosis of Escherichia coli and Staphylococcus aureus by neutrophils. Septic mice adoptively transferred with CD300ld-activated neutrophils exhibited markedly reduced bacterial loads in the blood and peritoneum, decreased inflammatory cytokine levels, and alleviated organ injury. These findings highlight the critical role of CD300ld signaling in neutrophil-mediated bacterial clearance in sepsis and provide a solid foundation for future research aimed at developing novel immunotherapies against this deadly disease condition.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078568","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":"Ferroptosis in neutrophils.","authors":"Yu-Bin Lee, Hyeong-Wook Shin, Sanjeeb Shrestha, Jun-Kyu Kim, Soo-Jung Jung, Min-Sang Shin, Chang-Won Hong","doi":"10.1093/jleuko/qiaf039","DOIUrl":"10.1093/jleuko/qiaf039","url":null,"abstract":"<p><p>Ferroptosis is a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation. The ferroptosis mechanism involves complex interactions between fatty acid metabolism, iron metabolism, lipid peroxidation, and antioxidative defense mechanisms. Fatty acids, especially polyunsaturated fatty acids, are susceptible to peroxidation, leading to the formation of lipid peroxides. Iron metabolism plays a critical role, as excessive free iron catalyzes the production of reactive oxygen species via the Fenton reaction, further promoting lipid peroxidation. Antioxidative mechanisms, including glutathione peroxidase 4 and other components of the glutathione system, are crucial for neutralizing lipid peroxides and preventing ferroptosis. Recent studies have highlighted the role of ferroptosis in neutrophils, particularly under pathological conditions. Neutrophils, due to their high iron content and abundance of polyunsaturated fatty acids, are inherently predisposed to ferroptosis. Recent studies indicate that polymorphonuclear myeloid-derived suppressor cells and tumor-infiltrating neutrophils exhibit high susceptibility to ferroptosis due to a dysregulated antioxidant defense mechanism through hypoxia-mediated downregulation of glutathione peroxidase 4. Conversely, tumor-infiltrating neutrophils resist ferroptosis through nuclear factor erythroid 2-related factor 2-dependent antioxidant pathway. Moreover, neutrophils induce ferroptosis in various cell types, such as endothelial cells, smooth muscle cells, and cardiomyocytes, through the release of neutrophil extracellular traps. This neutrophil extracellular trap-mediated ferroptosis contributes to the pathogenesis of conditions such as intestinal ischemia-reperfusion injury, aortic aneurysm, acute lung injury, and doxorubicin-induced cardiotoxicity. This review consolidates current knowledge on the mechanisms of ferroptosis in neutrophils and its implications in disease progression and immune regulation. Understanding these processes may provide new therapeutic targets for modulating immune responses and improving outcomes in ferroptosis-related diseases.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788517","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 complex immune exchange between mother and child continues to reveal surprising intricacies.","authors":"Licia Torres, Juan Miranda Peixoto, Tatiani Uceli Maioli","doi":"10.1093/jleuko/qiaf041","DOIUrl":"10.1093/jleuko/qiaf041","url":null,"abstract":"","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015377","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":"UDP-glucose regulates dendritic cell mitochondrial respiration via a nitric oxide-dependent mechanism.","authors":"Bay Vagher, Soyeon K Gullickson, Julia P Snyder, Tyler Hogan, Roxana Del Rio-Guerra, Keke C Fairfax, Eyal Amiel","doi":"10.1093/jleuko/qiaf047","DOIUrl":"10.1093/jleuko/qiaf047","url":null,"abstract":"<p><p>Bone marrow-derived dendritic cell (BMDC) activation is associated with rewiring of cellular metabolism and concurrent large-scale changes in gene expression promoting a proinflammatory program characterized by expression of inducible nitric oxide synthase and the production of nitric oxide (NO). NO inhibits vital cellular activities including mitochondrial respiration. Mitochondrial respiration inhibition via NO occurs at discrete levels of activating stimulus, termed the mitochondrial respiration threshold, and regulation of this threshold is not fully understood. In this work, we characterize the role of uridine diphosphate glucose as a modulator of NO-mediated mitochondrial respiration inhibition via P2Y14 receptor signaling in stimulated BMDCs. We demonstrate that BMDCs exhibit an enhanced proinflammatory profile in the presence of uridine diphosphate glucose, providing evidence for a new NO regulatory axis in BMDCs. These studies highlight the importance of the growing body of literature supporting metabolites as signaling molecules in activating conditions thus allowing for better modeling of physiologically relevant contexts for myeloid cell encounters with microbial stimuli.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024456","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":"Distinct roles of PGE2 signaling via EP2 and EP4 in circulating pDCs: Implications for immune modulation in the tumor microenvironment.","authors":"Jorge Cuenca-Escalona, Mark W D Sweep, Mark A J Gorris, Tjitske Duiveman-de Boer, Alessandra Cambi, Georgina Flórez-Grau, Jolanda M de Vries","doi":"10.1093/jleuko/qiaf034","DOIUrl":"10.1093/jleuko/qiaf034","url":null,"abstract":"<p><p>Dendritic cells (DCs) play a pivotal role in orchestrating adaptive immunity in response to environmental cues such as prostaglandin E2 (PGE2). Tumors are known to establish a microenvironment rich in PGE2. Tumor-derived PGE2 is regarded as mediator of regulatory features in DCs, facilitating immune evasion and tumor progression. In DCs, the effects of PGE2 are mediated through the E-prostanoid receptor type 2 (EP2) and EP4. While the immunomodulatory effects of PGE2 signaling via EP2/4 in monocyte-derived DCs (moDCs) is well established, its role in human blood plasmacytoid DCs (pDCs) is poorly characterized. Therefore, in this study we investigated the effect of EP2 and EP4 signaling on pDC function, as well as the relevance of modulating these receptors in pDCs exposed to tumor-derived PGE2. Our findings reveal that EP2 and EP4 exhibit distinct functions in pDCs. PGE2-EP4 signaling mediates the upregulation of maturation markers (e.g., CD83 and HLA-DR), enhances a CCR7-based migratory function, impairs the production of proinflammatory mediators (e.g., interferon α and CXCL9), and stimulates the expansion of CD8 T cells with a marked suppressive phenotype. In contrast, PGE2-EP2 signaling hinders the upregulation of maturation markers and induces the expansion of CD8 T cells with a suppressive character. Additionally, using different in vitro tumor models, we show that EP2/4 blockade modulates the phenotype of pDCs exposed to tumor-derived PGE2. Together, these results identify the distinctive role of EP2 and EP4 signaling in pDCs and illustrate the potential therapeutic benefit of targeting this signaling axis to mitigate tumor-induced pDCs dysfunction.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670012","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":"Secretory IgA binding to FCRL3 triggers shared inflammatory cytokine secretion by human regulatory T cells and effector T cells.","authors":"Zachary Kraus, Shama Birla, Taylor Powell, Svetlana Petrovskaya, Frederick Mills, Jessica Dement-Brown, Casey Culhane, Kimia Dokhaee, Mate Tolnay","doi":"10.1093/jleuko/qiaf054","DOIUrl":"10.1093/jleuko/qiaf054","url":null,"abstract":"<p><p>Several human lymphocyte subsets express the novel secretory IgA receptor FCRL3 (Fc receptor-like 3). Secretory IgA binding to FCRL3 diminishes the inhibitory capacity of regulatory T cells and promotes a T helper 17-like phenotype. Here, we report that in CD4+ regulatory T cells and CD8+ terminal effector T cells secretory IgA induced a shared inflammatory gene signature that included PTGS2 encoding COX2, and the prototypic inflammatory cytokine genes IL1A, IL1B, and IL8. Secretory IgA in regulatory T cells also elevated gene transcripts required for lineage identity and function. Secretory IgA promoted interleukin (IL)-1β, IL-6, IL-8, IL-10, interferon γ, and tumor necrosis factor α protein secretion by both T cell types. Moreover, secretory IgA promoted NLRP3 inflammasome activation in regulatory T cells. Pharmacologic COX2 and NLRP3 inhibitors partially rescued the inhibitory competence of regulatory T cells, suggesting respective mechanistic roles. We propose that secretory IgA provokes a coordinated inflammatory response in regulatory and effector T cells to facilitate mucosal pathogen clearance.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017167","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":"Temporal immune profiling in the cerebrospinal fluid and blood of patients with aneurysmal subarachnoid hemorrhage.","authors":"Thomas A Ujas, Katie L Anderson, Jenny Lutshumba, Samantha N Hart, Jadwiga Turchan-Cholewo, Kevin W Hatton, Adam D Bachstetter, Barbara S Nikolajczyk, Ann M Stowe","doi":"10.1093/jleuko/qiaf038","DOIUrl":"10.1093/jleuko/qiaf038","url":null,"abstract":"<p><p>Delayed cerebral ischemia (DCI) is a significant complication of aneurysmal subarachnoid hemorrhage (aSAH). This study profiled immune responses after aSAH and evaluated their association with DCI onset. Twelve aSAH patients were enrolled. Leukocyte populations and cytokine levels were analyzed in cerebrospinal fluid (CSF) and peripheral blood (PB) on days 3, 5, 7, 10, and 14 post-aSAH. PB mononuclear cells (PBMCs) were collected, and their cytokine production quantified following stimulation. Mixed-effects models reveal distinct immune cell dynamics in CSF compared with blood. Monocyte/macrophage numbers continue to increase in both CSF and PBMCs for days post-aSAH. CD4+ human leukocyte antigen II+ T cells and CD8+ CD154+ T cells increased in circulation over time. Unstimulated PBMCs showed increased interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha production, peaking at 7 d post-aSAH, coinciding with typical DCI onset. Ex vivo stimulation of PBMCs showed that only IL-6 significantly changed over time. In CSF, cytokines peaked 5 d postinjury, preceding immune cell profile alterations. Our findings reveal a time-dependent immune response following aSAH, with distinct within-patient patterns in CSF and PB. The early CSF cytokine peak preceding immune cell changes suggests a potential mechanistic link and identifies the cytokine response as a potential therapeutic target. This cytokine surge may drive immune cell expansion and prime PBMCs for increased inflammatory activity, potentially contributing to DCI risk. Future studies should explore the importance and sources of specific cytokines in driving immune activation. These insights may inform the development of targeted immunomodulatory strategies for preventing or managing DCI in aSAH patients.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742988","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}