Journal of Leukocyte Biology最新文献_第6页

Single-cell RNA sequencing revealed the immunophenotypic features of macrophages in cardiac transplants and uncovered Lgals9 promoted their polarization toward the M2b subtype. 单细胞RNA测序揭示了心脏移植巨噬细胞的免疫表型特征，发现Lgals9促进了它们向M2b亚型的极化。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI: 10.1093/jleuko/qiaf009

Yuexing Zhu, Xinguo Zheng, Chao Chen, Ye Xu, Yuxi Fan, Zhouqi Tang, Yingqi Zeng, Chen Feng, Hedong Zhang, Xiaojun Chen, Zhongquan Qi, Tengfang Li, Longkai Peng, Minjie Lin, Weili Chen, Fenghua Peng, Xin Jiang, Helong Dai

{"title":"Single-cell RNA sequencing revealed the immunophenotypic features of macrophages in cardiac transplants and uncovered Lgals9 promoted their polarization toward the M2b subtype.","authors":"Yuexing Zhu, Xinguo Zheng, Chao Chen, Ye Xu, Yuxi Fan, Zhouqi Tang, Yingqi Zeng, Chen Feng, Hedong Zhang, Xiaojun Chen, Zhongquan Qi, Tengfang Li, Longkai Peng, Minjie Lin, Weili Chen, Fenghua Peng, Xin Jiang, Helong Dai","doi":"10.1093/jleuko/qiaf009","DOIUrl":"10.1093/jleuko/qiaf009","url":null,"abstract":"Macrophages (MAC) play a crucial role in the immune response during allograft rejection in organ transplantation. Therefore, our study aimed to explore the genomic features of MAC in mouse heart transplants and use single-cell RNA sequencing to investigate Galectin-9 (Gal-9 and Lgals9), a lectin that can mediate the activation and differentiation of immune cells through ligand-receptor interactions, and the effects of its regulation in transplantation. We discovered a new subset of MAC called \"Myoz2+ MAC,\" which specifically expressed genes related to myocardial contraction. We identified a distinct differentiation trajectory and process for the Saa3+ macrophage population, representing anti-inflammatory functionality. Also, we observed a significant downregulation of Lgals9 expression in the MAC after mouse heart transplantation. Then, we validated our findings using RT-qPCR and Western blotting and also investigated the impact of Lgals9 on macrophage function through flow cytometry and ELISA. Furthermore, in vitro, we found that rLgals9 (Recombinant Mouse Galectin-9 Protein) treated MAC polarized toward the M2b phenotype at appropriate concentrations.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006765","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

A method for screening functional anti-Treg antibodies using a Treg-like cell line. 利用treg样细胞系筛选功能性抗treg抗体的方法。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI: 10.1093/jleuko/qiae257

Kirsten Pfeffer, Thai H Ho, Yvette Ruiz, Douglas F Lake

{"title":"A method for screening functional anti-Treg antibodies using a Treg-like cell line.","authors":"Kirsten Pfeffer, Thai H Ho, Yvette Ruiz, Douglas F Lake","doi":"10.1093/jleuko/qiae257","DOIUrl":"10.1093/jleuko/qiae257","url":null,"abstract":"Regulatory T cells can suppress activated T-cell proliferation by direct cell contact, although the exact mechanism is poorly understood. Identification of a Treg-specific cell surface molecule that mediates suppression would offer a unique target for cancer immunotherapy to inhibit Treg immunosuppressive function or deplete Tregs in the tumor microenvironment. In this study, we explored a method of whole-cell immunization using a Treg-like cell line (MoT cells) to generate and screen monoclonal antibodies that bound cell surface proteins in their native conformations and functionally reversed Treg-mediated suppression. From the 105 hybridomas that bound to the MoT cell surface, a functional screen utilizing conventional Treg suppression assays revealed 32 candidate antibodies that exhibited functional activity (reversed or enhanced suppressive activity). As an example, we characterized 1 anti-MoT mAb, 12E7, that exhibited strong binding to MoT cells and conventional Treg cell surfaces. This candidate antibody was subsequently found to bind to a potential suppressive target, CD44, and demonstrated the ability to partially reverse MoT and conventional human Treg-mediated suppression.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909733","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

Fc gamma receptors activate different protein kinase C isoforms in human neutrophils. Fc γ受体可激活人中性粒细胞中不同的蛋白激酶 C 同工酶。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI: 10.1093/jleuko/qiaf019

Omar Rafael Alemán, Carlos Blanco-Camarillo, Nathalia Naranjo-Pinto, Nancy Mora, Carlos Rosales

{"title":"Fc gamma receptors activate different protein kinase C isoforms in human neutrophils.","authors":"Omar Rafael Alemán, Carlos Blanco-Camarillo, Nathalia Naranjo-Pinto, Nancy Mora, Carlos Rosales","doi":"10.1093/jleuko/qiaf019","DOIUrl":"10.1093/jleuko/qiaf019","url":null,"abstract":"Receptors for FcγR on human neutrophils constitute an important mechanism for the recognition of opsonized microorganisms and for cell activation. Human neutrophils express 2 FcγR: FcγRIIa and FcγRIIIb. Previously, it has been reported that activation of each FcγR induces different neutrophil responses by triggering distinct signal transduction pathways, although what particular signal transduction pathway is triggered by each FcγR has not been completely elucidated. It has also been reported that PKC is important for FcγR signaling and that each FcγR may activate different PKC isoforms. Therefore, we explored whether FcγRIIa or FcγRIIIb activates different PKC isoforms in human neutrophils and whether activation of these PKC isoforms results in different neutrophil responses. Hence, either FcγRIIa or FcγRIIIb was selectively cross-linked by monoclonal antibodies in the presence or absence of pharmacological inhibitors for various PKC isoforms. Inhibition of PKCα or PKCδ blocked FcγRIIa-induced reactive oxygen species productions. In contrast, inhibition of PKCα and/or PKCβ blocked FcγRIIIb-induced reactive oxygen species production. Also, inhibition of all PKC isoforms did not affect the FcγRIIa-induced increase in intracellular calcium concentration ([Ca2+]i), while inhibition of PKCα blocked FcγRIIIb-induced increase in [Ca2+]i. Additionally, inhibition of PKCδ blocked FcγRIIa-induced ERK phosphorylation, while inhibition of PKCα prevented FcγRIIIb-induced ERK phosphorylation. These results suggest that both FcγRIIa and FcγRIIIb activate unique PKC isoforms and that activation of these PKC isoforms can selectively regulate different neutrophil functions. These findings also reinforce the idea that each FcγR in human neutrophils triggers distinct signal transduction pathways.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414323","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

Adenosine accumulation in the blood of newborn mice weakens antimicrobial host defenses. 新生小鼠血液中腺苷的积累削弱了抗微生物宿主的防御。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI: 10.1093/jleuko/qiaf003

Carola Ledderose, Eleftheria-Angeliki Valsami, Mark Elevado, Ava Stevenson, Reem Abutabikh, Julian Curatolo, Wolfgang G Junger

{"title":"Adenosine accumulation in the blood of newborn mice weakens antimicrobial host defenses.","authors":"Carola Ledderose, Eleftheria-Angeliki Valsami, Mark Elevado, Ava Stevenson, Reem Abutabikh, Julian Curatolo, Wolfgang G Junger","doi":"10.1093/jleuko/qiaf003","DOIUrl":"10.1093/jleuko/qiaf003","url":null,"abstract":"Pediatric intensive care patients are particularly susceptible to severe bacterial infections because of ineffective neutrophil responses. The reasons why neutrophils of newborns are less responsive than those of adults are not clear. Because adenosine triphosphate and adenosine tightly regulate neutrophils, we studied whether the adenosine triphosphate and adenosine levels in the blood of newborn mice could impair the function of their neutrophils. We observed significant changes in plasma adenosine triphosphate and adenosine levels throughout the lifespan of mice. Adenosine levels in newborns were significantly higher than in older mice, while adenosine triphosphate levels were significantly lower. These changes were particularly striking in newborn and juvenile mice with adenosine triphosphate and adenosine levels of about 80 and 600 nM in newborns vs 130 and 190 nM in juveniles, respectively. The ratios of the adenosine triphosphate vs adenosine levels of newborns were (with 0.2) significantly lower than those of juveniles (1.4) and adults (0.5). These low adenosine triphosphate/adenosine ratios correlated with significantly weakened neutrophil activation responses following in vitro stimulation with a formyl peptide receptor agonist and a markedly higher morbidity and mortality rate of newborns following bacterial infection. We found that enhanced adenosine monophosphate hydrolysis via CD73, a lack of adenosine breakdown by adenosine deaminase, and reduced adenosine uptake by nucleoside transporters are responsible for the low adenosine triphosphate/adenosine ratios in blood of newborn mice. We conclude that the extracellular adenosine accumulation in newborn mice impairs inflammatory responses and reduces the ability of neutrophils to mount effective antimicrobial defenses against bacterial infections.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006529","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

Flow cytometric measurement of CFTR-mediated chloride transport in human neutrophils. cftr介导的人中性粒细胞氯离子转运的流式细胞术测定。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI: 10.1093/jleuko/qiaf006

Alejandra Montanez-Barragan, Frank H Robledo-Avila, Raul Rascon, Karen S McCoy, Benjamin T Kopp, Santiago Partida-Sanchez

{"title":"Flow cytometric measurement of CFTR-mediated chloride transport in human neutrophils.","authors":"Alejandra Montanez-Barragan, Frank H Robledo-Avila, Raul Rascon, Karen S McCoy, Benjamin T Kopp, Santiago Partida-Sanchez","doi":"10.1093/jleuko/qiaf006","DOIUrl":"10.1093/jleuko/qiaf006","url":null,"abstract":"Immune cells express a variety of ion channels and transporters in the plasma membrane and intracellular organelles, responsible of the transference of charged ions across hydrophobic lipid membrane barriers. The correct regulation of ion transport ensures proper immune cell function, activation, proliferation, and cell death. Cystic fibrosis (CF) is a genetic disease in which the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel gene is defective; consequently, the CFTR protein is dysfunctional, and the chloride efflux in CF cells is markedly impaired. CF is characterized by chronic inflammation in the airways, mainly triggered by neutrophilic infiltration and recurring bacterial infections, causing the decline of lung function and eventually respiratory failure. Novel modulator-based therapies have improved lung function in people with CF by increasing expression and function of CFTR in the plasma membrane of lung cells; however, the effects of these drugs in the lung-recruited inflammatory cells, specifically neutrophils, remains unknown. Given the complex biology of neutrophils and their short lifespan, we aimed to develop a fluorometric method to evaluate CFTR-mediated chloride transport in human neutrophils by using flow cytometry and the intracellular chloride-binding MQAE dye. Our results show that CFTR-mediated chloride transport in human neutrophils or human neutrophil-like cell lines can be consistently evaluated in vitro by this methodology. Additionally, this assay measured increased chloride efflux in neutrophils collected from people with CF under modulator therapy, as compared with healthy donors, indicating that this method can evaluate restoration of CFTR-mediated chloride transport in CF neutrophils.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006624","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

MiR-340-5p alleviates AECOPD by targeting MAP3K2 via Qingjin Huatan decoction therapy. MiR-340-5p通过清金化痰汤靶向MAP3K2治疗AECOPD。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI: 10.1093/jleuko/qiaf021

Mei Zhao, Zhijian Huang, Jinghui Zheng, Wanying Li, Yunqing Zhong, Tun Ouyang

{"title":"MiR-340-5p alleviates AECOPD by targeting MAP3K2 via Qingjin Huatan decoction therapy.","authors":"Mei Zhao, Zhijian Huang, Jinghui Zheng, Wanying Li, Yunqing Zhong, Tun Ouyang","doi":"10.1093/jleuko/qiaf021","DOIUrl":"10.1093/jleuko/qiaf021","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) features persistent inflammation and restricted airflow, with acute exacerbations of COPD (AECOPD) significantly worsening patient outcomes. This study aims to explore the role of Qingjin Huatan Decoction (QJHTT) on AECOPD with the syndrome of phlegm-heat obstruction of the lung. AECOPD was induced in male Sprague-Dawley rats using lipopolysaccharide and cigarette smoke exposure. Rats were treated with varying doses of QJHTT. miR-340-5p expression was quantified using qPCR. Lung histopathology was assessed with hematoxylin and eosin staining, and interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha were measured by enzyme-linked immunosorbent assay (ELISA). The effects on cell viability and apoptosis in primary airway epithelial cells were evaluated using Cell Counting Kit-8 and flow cytometry assays, respectively. The dual-luciferase reporter assay validated the interaction between miR-340-5p and mitogen-activated protein kinase kinase kinase 2 (MAP3K2), and protein expression was analyzed by Western blot. QJHTT improved lung histopathology, reducing inflammatory cell infiltration, and alveolar damage. ELISA results showed reduced inflammatory cytokine levels in QJHTT-treated groups (P < 0.05). qPCR analysis demonstrated that QJHTT upregulated miR-340-5p expression (P < 0.05). miR-340-5p mimic enhanced cell viability and reduced apoptosis in primary airway epithelial cells (P < 0.05). Dual-luciferase reporter assay confirmed that miR-340-5p directly targets MAP3K2, leading to its downregulation (P < 0.05). QJHTT exerts therapeutic effects in phlegm-heat obstructing the lung type of AECOPD through upregulating miR-340-5p and inhibiting MAP3K2. This study highlights the QJHTT and miR-340-5p/MAP3K2 pathway for this disease treatment.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458292","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

Nexinhib20 inhibits JFC1-mediated mobilization of a subset of CD11b/CD18+ vesicles decreasing integrin avidity, but does not inhibit Rac1. Nexinhib20抑制jfc1介导的CD11b/CD18+囊泡亚群的动员，降低整合素的亲和力，但不抑制Rac1。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI: 10.1093/jleuko/qiaf012

Kasra Askari, Jennifer L Johnson, Aparna Shukla, Elsa Meneses-Salas, William B Kiosses, Juan Yu, Sergio D Catz

{"title":"Nexinhib20 inhibits JFC1-mediated mobilization of a subset of CD11b/CD18+ vesicles decreasing integrin avidity, but does not inhibit Rac1.","authors":"Kasra Askari, Jennifer L Johnson, Aparna Shukla, Elsa Meneses-Salas, William B Kiosses, Juan Yu, Sergio D Catz","doi":"10.1093/jleuko/qiaf012","DOIUrl":"10.1093/jleuko/qiaf012","url":null,"abstract":"Regulated sequential exocytosis of neutrophil granules is essential for orchestrating the innate immune response, while uncontrolled secretion causes inflammation. We developed and characterized Nexinhib20, a small-molecule inhibitor that targets azurophilic granule exocytosis in neutrophils by blocking the interaction between the small GTPase Rab27a and its effector JFC1. Its therapeutic potential has been demonstrated in several preclinical models of inflammatory disease. Here, using neutrophils from Jfc1-KO mice, we show that JFC1 regulates the mobilization of a small subpopulation of CD11b+ granules. Nexinhib20 inhibits the mobilization of β2-integrins from a subset of CD11b+ granules to the plasma membrane in human and mouse neutrophils. The putative impact of Nexinhib20 on integrin activation is caused by decreased avidity, secondary to its effect on β2-integrin mobilization. CD11b mobilization and integrin activation were unaffected by pharmacological inhibition or activation of Rac1. Using quantitative 3D enhanced resolution microscopy, we show that neutrophil activation induces the recruitment of JFC1 to CD11b+ granules. Nexinhib20 decreased the localization of JFC1 at CD11b+ granules without affecting the association of Rac1 with CD11b. Nexinhib20 inhibits JFC1 recruitment but not endogenous Rac1 activation in living cells. Using orthogonal analyses of Rac1 activity consisting of a sensitive, time-resolved fluorescence energy transfer, Rac1-PAK1-binding assay, and endogenous Rac1-GTP examination, we show that Nexinhib20 does not interfere with Rac1 activation. Instead, we confirm its molecular mode of action as the inhibition of the Rab27a-JFC1 binding. Thus, Nexinhib20 limits β2-integrin mobilization to the cell surface, decreasing avidity and affecting active integrin availability in a JFC1-dependent but Rac1-independent manner.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066060","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

Thymic eosinophils: What are you doing here? 胸腺嗜酸性粒细胞：你在这里做什么？

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI: 10.1093/jleuko/qiaf001

Dominique M Gatti, Lisa A Reynolds

引用次数: 0

Neutrophil extracellular traps capture the human pathogen, Candida albicans, in blood and delay hyphal transformation. 中性粒细胞胞外陷阱捕获人类病原体，白色念珠菌，在血液和延迟菌丝转化。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI: 10.1093/jleuko/qiaf002

Miyuki Sakuma, Adam Viens, Alex Hopke, Daniel J Floyd, Musie Ghebremichael, Michael K Mansour, Daniel Irimia

引用次数: 0

Apolipoprotein E aggregation in microglia, seeds β-amyloidosis in Alzheimer's disease. APOE聚集在小胶质细胞，阿尔茨海默病的种子b-淀粉样变。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI: 10.1093/jleuko/qiaf007

Miguel A Jiménez-Acosta, Cristina A Luckie-Duque, Marco A Meraz-Ríos

引用次数: 0