Journal of Leukocyte Biology最新文献_第3页

Resolution of Innate Immune Cells with Pro-Resolving Lipid Mediators in Idiopathic Pulmonary Fibrosis. 先天免疫细胞与促溶解脂质介质在特发性肺纤维化中的溶解

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-07-03 DOI: 10.1093/jleuko/qiaf100

Yuet Ang, Ashton J K Ng, Wupeng Liao, K Y Kevin Wong, W S Fred Wong, Hong Yong Peh

{"title":"Resolution of Innate Immune Cells with Pro-Resolving Lipid Mediators in Idiopathic Pulmonary Fibrosis.","authors":"Yuet Ang, Ashton J K Ng, Wupeng Liao, K Y Kevin Wong, W S Fred Wong, Hong Yong Peh","doi":"10.1093/jleuko/qiaf100","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf100","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a progressive incurable lung disease characterized by chronic inflammation and fibrosis, with innate immune cells such as neutrophils and macrophages playing central roles in its pathogenesis. This review explores the involvement of these immune cells in the inflammatory process of IPF, focusing on their contribution to disrupted tissue repair and impaired resolution. The balance between host defense mechanisms, including leukocyte recruitment, and the release of pro-resolving mediators is crucial for maintaining healthy tissue function and returning to pre-inflammatory states. We highlight the importance of inflammation resolution to prevent an overactive immune response, which can lead to irreversible fibrosis. Specialized pro-resolving mediators (SPMs), including lipoxins, resolvins, protectins, and maresins, are discussed in terms of their regulatory effects on neutrophils and macrophages in IPF. These mediators exhibit potent anti-inflammatory actions, which can modulate the immune response and promote the resolution of inflammation. Overall, this review underscores the significance of immune modulation in IPF, with a focus on the therapeutic potential of SPMs in controlling the inflammatory response and preventing fibrosis progression. Future research into the anti-fibrotic properties of SPMs and their impact on innate immune cell regulation holds promise for novel therapeutic strategies in IPF treatment.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553706","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

Ageing affects the CD4+ T cell polarization and mucosal tropism induced by TLR2/TLR4-activated dendritic cells. 衰老影响TLR2/ tlr4激活的树突状细胞诱导的CD4+ T细胞极化和粘膜倾向。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-06-27 DOI: 10.1093/jleuko/qiaf096

Sara Zúquete, Mariana Ferreira, Inês L S Delgado, Maria Teresa Rosa, Ana Catarina Mendes, Dulce Santos, Sofia Nolasco, Luís Graça, Alexandre Leitão, Afonso P Basto

{"title":"Ageing affects the CD4+ T cell polarization and mucosal tropism induced by TLR2/TLR4-activated dendritic cells.","authors":"Sara Zúquete, Mariana Ferreira, Inês L S Delgado, Maria Teresa Rosa, Ana Catarina Mendes, Dulce Santos, Sofia Nolasco, Luís Graça, Alexandre Leitão, Afonso P Basto","doi":"10.1093/jleuko/qiaf096","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf096","url":null,"abstract":"Toll-like receptor (TLR)2 activation induces aldehyde dehydrogenase enzymes in non-mucosal dendritic cells (DCs) enabling them to metabolize vitamin A into all-trans retinoic acid, which induces the expression of mucosal-homing molecules (α4β7 and CCR9) in the activated T cells. Recently, we have shown that the simultaneous activation of non-mucosal DCs through TLR2 and TLR4 maintains such capacity while reinforcing the polarization of primed CD4+ T cells towards Th1. Here, we observed that TLR2/TLR4 stimulation of aged DCs leads to the production of less TNFα and more IL-10 and that CD4+ T cells primed by those DCs express lower levels of the mucosal homing receptor CCR9 and produce less type-1 (IFNγ) and more type-2 (IL-4 and IL-13) cytokines. These results emphasize the importance of considering the age-related alterations in DC function when developing novel immunomodulation strategies that rely on the DC-T cell crosstalk through stimulation of pattern recognition receptors.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505981","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

Megakaryocyte emperipolesis in myeloproliferative neoplasms: are neutrophils friends or foes? 骨髓增殖性肿瘤中的巨核细胞增多：中性粒细胞是朋友还是敌人？

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-06-25 DOI: 10.1093/jleuko/qiaf093

Ryan J Collinson, Matthew D Linden, Kathryn A Fuller, Lynne Wilson, Bob Mirzai, Darren Boey, Zi Y Ng, Hun S Chuah, Jacques A J Malherbe, Rebecca Howman, Michael F Leahy, M Hasib Sidiqi, Janine H Collins, Willem H Ouwehand, Wendy N Erber, Belinda B Guo

{"title":"Megakaryocyte emperipolesis in myeloproliferative neoplasms: are neutrophils friends or foes?","authors":"Ryan J Collinson, Matthew D Linden, Kathryn A Fuller, Lynne Wilson, Bob Mirzai, Darren Boey, Zi Y Ng, Hun S Chuah, Jacques A J Malherbe, Rebecca Howman, Michael F Leahy, M Hasib Sidiqi, Janine H Collins, Willem H Ouwehand, Wendy N Erber, Belinda B Guo","doi":"10.1093/jleuko/qiaf093","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf093","url":null,"abstract":"Megakaryocyte emperipolesis is a biological process in which a cell penetrates and exists as a viable intact cell within another. It is a recognized morphological feature of myeloproliferative neoplasms (MPN), where neutrophils can be seen within megakaryocytes in bone marrow smears and sections. We aimed to determine whether neutrophil contents, specifically protein and RNA, are deposited within megakaryocytes due to emperipolesis. Evaluation of hematoxylin and eosin-stained bone marrow showed that 84% of MPN patients (n = 163) had megakaryocyte emperipolesis, most notably in enlarged megakaryocytes and those with pyknotic/condensed nuclei. Morphological assessment and immunohistochemical staining for CD15-neutrophil membrane antigen confirmed that majority of intra-megakaryocytic cells were neutrophils, and that emperipolesis was more frequent in MF patients and patients with pathologic reticulin. Furthermore, megakaryocytes in MPN were observed to have intracellular positivity for neutrophil azurophilic granule protein myeloperoxidase (MPO) (n = 21 MPN patients) and specific granule lactoferrin (LTF) (n = 56). Platelets were also used as a surrogate to establish if neutrophil contents had been transferred into megakaryocytes intracellularly of MPN patients, using mass spectrometry to assess protein and transcriptomic NGS to assess mRNA. 109 neutrophil mRNA transcripts and 20 neutrophil granule proteins were upregulated in platelets of MPN patients compared to controls, including cathepsin-G (CTSG) and LTF, with 5.1- and 4.6-fold increase in mRNA and 1.8- and 1.4-fold protein increases respectively. This suggests the transfer of neutrophil material occurs during emperipolesis in disease state, which could be a consequence of neutrophil degranulation or apoptosis.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497334","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

Metainflammation alters neutrophil function and migration in vivo in response to tissue injury. 间皮炎改变中性粒细胞功能和迁移在体内响应组织损伤。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-06-25 DOI: 10.1093/jleuko/qiaf094

Cassia Michael, Joaquin Canton Sandoval, Maria Feliz-Norberto, Pablo Scharf, Sofia de Oliveira

{"title":"Metainflammation alters neutrophil function and migration in vivo in response to tissue injury.","authors":"Cassia Michael, Joaquin Canton Sandoval, Maria Feliz-Norberto, Pablo Scharf, Sofia de Oliveira","doi":"10.1093/jleuko/qiaf094","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf094","url":null,"abstract":"Overnutrition and the consumption of Western-type diets lead to chronic low-grade systemic inflammation (i.e., metainflammation) and a dysfunctional immune response. Although neutrophils are affected by metainflammation, mechanistic evidence regarding the direct effects of dietary fat exposure on neutrophil function and migration in vivo, particularly in response to injury, remains limited. Here, we investigated how metainflammation induced by a high-cholesterol diet (HCD) influences neutrophil function and migration following tissue injury. We employed a tailfin transection model in juvenile zebrafish larvae with fluorescently tagged neutrophils fed an HCD and assessed neutrophil function and migration dynamics in vivo at the injury site and whole animal. We combined long-term, non-invasive intravital confocal microscopy with computational analysis to examine neutrophil behavior, and photoconversion techniques were used to track neutrophil mobilization across the larvae. Exposure to HCD resulted in a dysfunctional neutrophil response characterized by exacerbated recruitment, increased ROS production and NETosis, impaired apoptosis, and delayed inflammation resolution. Neutrophil forward and reverse migration were also significantly impacted at the injury site. Moreover, we identified diet-inflamed regions such as the liver and intestine as sources of activated neutrophils that reverse-migrate and respond to injuries at distant sites, contributing to inter-organ transmission of inflammation. Finally, ameliorating steatosis and systemic chronic inflammation rescued the exaggerated neutrophil recruitment to injury. Overall, our study highlights the crucial role of neutrophil dysregulation and reverse migration from diet-induced inflamed tissues in driving exaggerated and dysfunctional inflammatory responses to injury, providing insight into potential therapeutic strategies to alleviate these effects in metabolic disease.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484754","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

The role of liver macrophages in viral liver pathogenesis. 肝巨噬细胞在病毒性肝发病中的作用。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-06-25 DOI: 10.1093/jleuko/qiaf088

Alexis Brantly, Kyle Yeakle, Michael Bouchard, Peter J Gaskill, Michael R Nonnemacher

{"title":"The role of liver macrophages in viral liver pathogenesis.","authors":"Alexis Brantly, Kyle Yeakle, Michael Bouchard, Peter J Gaskill, Michael R Nonnemacher","doi":"10.1093/jleuko/qiaf088","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf088","url":null,"abstract":"Liver macrophages play important roles in the pathophysiology of liver fibrosis and hepatocellular carcinoma (HCC). However, liver macrophages are a heterogenous population and have differing roles in maintenance of liver function and response in disease. In a healthy liver, macrophages play a critical role in antigen processing, maintaining tolerance to the high levels of gut-derived bacterial products, and regulating inflammation through cytokine response. However, macrophages also play a critical role in liver pathology, specifically in the context of viral infection. The liver is targeted by multiple viruses, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), which dysregulate macrophage functions to affect liver disease. Infection with any of these viruses is associated with increased risk of developing HCC, and co-infection further accelerates the progression to liver disease and cancer. However, the exact mechanisms by which liver macrophages contribute to disease in the context of viral infections are not well defined. This is a particularly acute issue in HIV-infected populations, which have high incidence of HBV- and HCV-coinfection. To address this knowledge gap, this review describes the populations of macrophages in the liver, outlines the current models and limitations associated with the study of liver macrophages, discusses the function and role of liver macrophages in the context of viral infection, and describes the mechanisms by which these cells contribute to HCC and fibrosis. We then use this information to propose focus areas for the liver macrophage field to better address and resolve viral liver disease.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497335","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

Downregulation of miR-93 Inhibits Proliferation and Promotes Apoptosis and Hematopoiesis in Myelodysplastic Syndrome Cells through PAG1-Mediated EGFR Signaling Pathway. 下调miR-93通过pag1介导的EGFR信号通路抑制骨髓增生异常综合征细胞增殖，促进细胞凋亡和造血

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-06-18 DOI: 10.1093/jleuko/qiaf083

Junyu Liu, Hua Wang, Caihua Zhang

{"title":"Downregulation of miR-93 Inhibits Proliferation and Promotes Apoptosis and Hematopoiesis in Myelodysplastic Syndrome Cells through PAG1-Mediated EGFR Signaling Pathway.","authors":"Junyu Liu, Hua Wang, Caihua Zhang","doi":"10.1093/jleuko/qiaf083","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf083","url":null,"abstract":"MicroRNA-93 (miR-93) has been implicated in the pathogenesis of myelodysplastic syndrome (MDS), though its precise role in the regulation of hematopoiesis and cell fate in MDS remains poorly understood. This study aimed to investigate the impact of miR-93 on cell proliferation, apoptosis, and hematopoiesis in MDS, focusing on the PAG1-mediated EGFR signaling pathway. Bioinformatic analyses were used to identify the miR-93-PAG1-EGFR axis in MDS. Gain- and loss-of-function experiments were performed using miR-93 mimics, miR-93 inhibitors, and siRNA targeting PAG1 to evaluate their roles in MDS progression. Bone marrow mononuclear cells from MDS patients were analyzed to assess the molecular expression patterns. Our findings revealed elevated miR-93 expression and reduced PAG1 levels, alongside activation of the EGFR signaling pathway in MDS patient samples. Downregulation of miR-93 or activation of PAG1 reversed these molecular alterations. Specifically, reduced miR-93 levels led to decreased EGFR phosphorylation and upregulation of PAG1 expression, which resulted in suppressed MDS cell proliferation, increased apoptosis, and enhanced hematopoiesis. Furthermore, the expression of key signaling molecules, including c-fos, TNF-α, IL-3, and SCF, was modulated in response to miR-93 or PAG1 regulation. This study demonstrates that downregulation of miR-93 suppresses MDS progression through the inactivation of the EGFR signaling pathway and the upregulation of PAG1. Our results suggest that targeting the miR-93/PAG1/EGFR axis could offer potential therapeutic strategies for managing MDS and promoting hematopoiesis.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505982","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

Complexity of the neutrophil transcriptome in early and severe rheumatoid arthritis. A role for microRNAs? 早期和重度类风湿关节炎中性粒细胞转录组的复杂性。微rna的作用？

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-06-18 DOI: 10.1093/jleuko/qiaf090

Michele Fresneda Alarcon, Genna Ali Abdullah, John Alexander Beggs, Isobel Kynoch, Andrew Sellin, Andrew Cross, Sam Haldenby, Philipp Antczak, Eva Caamaño Gutiérrez, Helen Louise Wright

{"title":"Complexity of the neutrophil transcriptome in early and severe rheumatoid arthritis. A role for microRNAs?","authors":"Michele Fresneda Alarcon, Genna Ali Abdullah, John Alexander Beggs, Isobel Kynoch, Andrew Sellin, Andrew Cross, Sam Haldenby, Philipp Antczak, Eva Caamaño Gutiérrez, Helen Louise Wright","doi":"10.1093/jleuko/qiaf090","DOIUrl":"10.1093/jleuko/qiaf090","url":null,"abstract":"Neutrophils are innate immune cells that drive the progression of rheumatoid arthritis (RA) through the release of reactive oxygen species (ROS), neutrophil extracellular traps (NETs) and proteases that damage host tissues. Neutrophil activation is regulated, in part, by dynamic changes in gene expression. In this study we have used RNAseq to measure the transcriptomes of neutrophils from people with severe, methotrexate-refractory RA and healthy controls. We identified a dynamic gene expression profile in people with severe RA. This is dominated by a type-I interferon-induced gene expression signature as well as activation of genes regulating neutrophil degranulation, NET production, response to ROS and oxidative stress. Whilst we did not detect significantly elevated levels of interferon-alpha in RA blood sera, we identified increased expression in RA neutrophils of miR-96-5p and miR-183-5p which regulate activation of the interferon pathway as members of the miR-183C cluster. We also detected significantly elevated NET debris in RA blood sera (p<0.05). Using gene set variation analysis we explored the heterogeneity of neutrophil gene expression in RA and identified subsets of patients with gene expression profiles reflecting enhanced neutrophil degranulation and cytotoxicity, tissue inflammation or activation by interferons. Comparison with published single-cell RNAseq datasets identified RA transcriptomes where neutrophils were polarised by genes relating to early or late cell maturity, with significant genes in each polarised state being regulated by miR-146a-5p, miR-155-5p, miR-183-5p or miR-96-5p. Overall our study demonstrates the heterogeneity of the RA neutrophil transcriptome and proposes miRNA-driven mechanisms for regulating the activated neutrophil phenotype in RA.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511991","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

Pre-Ligand Assembly Domain-Derived Recombinant Proteins of TNFR2 Inhibits the Expansion of CD4+Foxp3+ Regulatory T Cells. TNFR2预配体组装域衍生重组蛋白抑制CD4+Foxp3+调节性T细胞的扩增

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-06-18 DOI: 10.1093/jleuko/qiaf087

Wen-Wei Li, Chuangen Li, Yang Yang, Yibo Chen, Zhonghao Chen, Yang Gao, Yiru Wang, Tao Liu, Xin Chen, Chon-Kit Chou

{"title":"Pre-Ligand Assembly Domain-Derived Recombinant Proteins of TNFR2 Inhibits the Expansion of CD4+Foxp3+ Regulatory T Cells.","authors":"Wen-Wei Li, Chuangen Li, Yang Yang, Yibo Chen, Zhonghao Chen, Yang Gao, Yiru Wang, Tao Liu, Xin Chen, Chon-Kit Chou","doi":"10.1093/jleuko/qiaf087","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf087","url":null,"abstract":"There is compelling evidence that tumor necrosis factor (TNF) receptor type II (TNFR2) mediates the stimulatory effect of TNF on the activation of CD4+Foxp3+ regulatory T cells (Tregs). Tregs with high TNFR2 expression are critical components of tumor microenvironment (TME), where they promote tumor progression by impeding anti-tumor immune responses. Thus, selectively targeting TNFR2 has emerged as a promising strategy to inhibit Treg activity and enhance anti-tumor immune responses. The pre-ligand-binding assembly domain (PLAD) is a conserved extracellular domain that subtly differs among TNF receptor family members, facilitating the ligand-independent assembly of receptor monomers into a spatially optimal trimer that favors ligand binding. Previous studies demonstrated that recombinant PLAD proteins derived from TNFR1 were able to inhibit TNFR1-mediated cell death and alleviated inflammatory conditions in mouse models. However, the functional properties of TNFR2-derived PLAD remain largely unexplored. In this study, we developed recombinant PLAD proteins from human and mouse TNFR2, as well as TNFR1, and evaluated their ability to interfere with TNF binding and Treg activation. All four PLAD proteins dose-dependently inhibited TNF-stimulated NF-κB transcriptional activity in HEK293 reporter cells. Among them, human TNFR2-derived PLAD exhibited relatively enhanced inhibitory effects compared to the other three in HEK293 reporter cells overexpressing TNFR2 but lacking TNFR1, and potently blocked TNF binding to TNFR2 on Jurkat cell surfaces. Furthermore, human TNFR2-derived PLAD significantly reduced the TNF-induced proliferative expansion of CD4+Foxp3+ Tregs in both mouse lymphocyte and human peripheral blood mononuclear cell (PBMC) cultures. Our findings suggest that human TNFR2-derived PLAD merits further investigation for the cancer immunotherapy.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505983","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

Granulocyte function in response to acute alcohol consumption: temporal shifts from proinflammatory activation to antiinflammatory modulation in healthy volunteers. 粒细胞功能对急性饮酒的反应：健康志愿者从促炎激活到抗炎调节的时间转变

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-06-04 DOI: 10.1093/jleuko/qiaf081

Ramona Sturm, Florian Haag, Helen Rinderknecht, Jasmin Maria Bülow, Nils Wagner, Julian Zabel, Christian B Bergmann, Ingo Marzi, Borna Relja

{"title":"Granulocyte function in response to acute alcohol consumption: temporal shifts from proinflammatory activation to antiinflammatory modulation in healthy volunteers.","authors":"Ramona Sturm, Florian Haag, Helen Rinderknecht, Jasmin Maria Bülow, Nils Wagner, Julian Zabel, Christian B Bergmann, Ingo Marzi, Borna Relja","doi":"10.1093/jleuko/qiaf081","DOIUrl":"10.1093/jleuko/qiaf081","url":null,"abstract":"While chronic alcohol use is proinflammatory, the immune effects of acute intake remain unclear. We examined granulocyte responses to binge drinking, common in youth. Twenty-two volunteers consumed 12 alcoholic drinks over 4 h (blood alcohol concentration 1.0‰). Blood was collected at baseline (T0), 2 h (T2), 4 h (T4), 6 h (T6), 24 h (T24), and 48 h (T48) postintake. Interleukin (IL)-6 and M30 (inflammation, cell death) were analyzed by enzyme-linked immunosorbent assay; CXCL10 and MPO gene expression in polymorphonuclear leukocytes (PMNLs) by qRT-PCR; CD62L and Toll-like receptor (TLR4) on CD16+ granulocytes by flow cytometry; inflammasome activation post-LPS/ATP stimulation; and PMNL adhesion to A549 lung cells. IL-6 increased significantly at T2 to T6; M30 peaked at T4, decreasing at T24 and T48. CXCL10 and MPO increased at T2 and T4; MPO declined at T24 and T48. TLR4-positive granulocytes increased at T2 and T4. Active caspase-1 rose over 48 h, while stimulated activation declined at T4 and T24. CD62L increased at T2 before declining. PMNL adhesion decreased significantly at T24 and T48. Acute alcohol triggers early inflammation followed by immune suppression.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248274","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

TIPE regulates TGFB2 expression and induces extracellular M2 polarization in CRC. TIPE调节CRC中TGFB2的表达，诱导细胞外M2极化。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-06-04 DOI: 10.1093/jleuko/qiaf066

Qiang Zhu, Shiying Zhang, Changxiu Yan, Zeyang Lin, Shuaishuai Zhang, Haoyang Li, Yuhan Ye, Zhongchen Liu, Guohong Zhuang, Kun Zhang

{"title":"TIPE regulates TGFB2 expression and induces extracellular M2 polarization in CRC.","authors":"Qiang Zhu, Shiying Zhang, Changxiu Yan, Zeyang Lin, Shuaishuai Zhang, Haoyang Li, Yuhan Ye, Zhongchen Liu, Guohong Zhuang, Kun Zhang","doi":"10.1093/jleuko/qiaf066","DOIUrl":"10.1093/jleuko/qiaf066","url":null,"abstract":"The immunosuppressive tumor microenvironment (TME) is a critical determinant of therapeutic resistance in colorectal cancer (CRC). The TME encompasses diverse cellular and stromal elements, including tumor cells, immune cells, extracellular matrix, and lymphatic vessels. Among these components, tumor-associated macrophages predominate both quantitatively and functionally, with M2-polarized macrophages being the principal subset responsible for immunosuppression. Identifying genes that promote M2 polarization from CRC would provide a more targeted approach to addressing this issue at its root. In this study, we demonstrate that TIPE derived from CRC indirectly stimulates extracellular M2 polarization. Mechanistically, TIPE activates the P38 MAPK signaling pathway, leading to increased expression and secretion of TGFB2, which subsequently acts on extracellular macrophages to induce M2 polarization. Moreover, M2 macrophages polarized by CRC-derived factors exert a feedback loop that enhances CRC proliferation, migration, and invasion, with the effect intensifying as TIPE expression in CRC increases. Animal experiments have also revealed that TGFB2 induced by TIPE can disseminate systemically via the bloodstream, influencing not only peritumoral macrophages but also inducing M2 polarization in macrophages in distant organs. Collectively, our findings indicate that TIPE from CRC can indirectly polarize extracellular macrophages to an M2 phenotype, thereby amplifying the malignant behavior of CRC.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101954","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