Kai-Cheng Gao, Hao Li, Dan Liang, Shuang-Xiu Li, Lin Yang, Yu Zhao, Yi-Qun Kuang
{"title":"E26 transformation-specific-1 controls asthma development by regulating the CD4+ Th2/Th17 immune response involved transcription factors in active genomic transcriptional regions.","authors":"Kai-Cheng Gao, Hao Li, Dan Liang, Shuang-Xiu Li, Lin Yang, Yu Zhao, Yi-Qun Kuang","doi":"10.1093/jleuko/qiaf032","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf032","url":null,"abstract":"<p><p>Asthma is a chronic respiratory disease characterized by airway inflammation and immune cell imbalance. The transcription factor E26 transformation-specific-1 regulates immune cell functions, but its role in asthma remains unclear. Here, we generated Ets1 heterozygous (Ets1+/-) mice by constitutively knocking out exons 7 and 8 of Ets1, confirmed significantly reduced Ets1 expression via western blot. Asthma models were then established in both wild-type and Ets1+/- mice, revealing more severe pulmonary inflammation in Ets1+/- mice. Then, we systematically explored the regulatory effects of Ets1 on immune cells function and inflammatory responses in asthma. Further analyses showed enhanced CD4+ helper T (Th) 2/Th17 cell responses and elevated interleukin-4 and interleukin-17A secretion in the asthma Ets1+/- mice. By combining chromatin immunoprecipitation sequencing and RNA sequencing analyses, we identified 17 transcription factors regulated by Ets1 and linked to the function of mitotic processes in asthma. These findings suggest that Ets1 mitigates asthma by modulating CD4+ Th2/Th17 immune responses and regulating transcription factors associated with cell cycle processes.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"117 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076976","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}
Dan Hao, Margaret A McBride, Julia K Bohannon, Antonio Hernandez, Benjamin Klein, David L Williams, Edward R Sherwood
{"title":"Metabolic adaptations driving innate immune memory: mechanisms and therapeutic implications.","authors":"Dan Hao, Margaret A McBride, Julia K Bohannon, Antonio Hernandez, Benjamin Klein, David L Williams, Edward R Sherwood","doi":"10.1093/jleuko/qiaf037","DOIUrl":"10.1093/jleuko/qiaf037","url":null,"abstract":"<p><p>Immune memory is a hallmark of the adaptive immune system. However, recent research reveals that innate immune cells also retain memory of prior pathogen exposure that prompts enhanced responses to subsequent infections. This phenomenon is termed \"innate immune memory\" or \"trained immunity.\" Notably, remodeling of cellular metabolism, which closely links to epigenetic reprograming, is a prominent feature of innate immune memory. Adaptations in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, glutaminolysis, and lipid synthesis pathways are critical for establishing innate immune memory. This review provides an overview of the current understanding of how metabolic adaptations drive innate immune memory. This understanding is fundamental to understanding innate immune system functions and advancing therapies against infectious 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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730335","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":"Mitochondrial fusion reduces T cell susceptibility to HIV infection through citrate modulation.","authors":"Zichen Song, Jiangrong Wang, Zhihang Zheng, Zhixiang He, Jingna Xun, Ling Gu, Yinzhong Shen, Jun Chen","doi":"10.1093/jleuko/qiaf042","DOIUrl":"10.1093/jleuko/qiaf042","url":null,"abstract":"<p><p>Inhibiting the metabolic activity of CD4+ T cells can effectively reduce human immunodeficiency virus (HIV) infection. Mitochondria, as critical organelles in eukaryotic metabolism, play a significant role in the progression of many diseases. The change of mitochondrial dynamics is an important process of mitochondrial regulation of cell metabolic activity. However, it remains uncertain whether regulating mitochondrial dynamics is a viable approach to reducing HIV infection. In this study, we demonstrated that promoting mitochondrial fusion in Jurkat cells through treatment with the mitochondrial fusion promoter M1 and the Drp1 (dynamin-related protein 1) inhibitor Mdivi1 conferred resistance to single-round VSVG-HIVNL4-3-GFP viral infection. Targeted metabolomics analysis revealed and subsequently confirmed the potential involvement of citrate in reducing HIV infection, which has been subsequently verified. Further, we found that plasma citrate level was negatively associated with HIV disease progression. Multiomics results showed that citric acid leads to a decrease in the level of nucleotide metabolism in Jurkat cells. In conclusion, increased citrate levels resulting from mitochondrial fusion significantly impair the ability of HIV to infect cells, which may be due to regulated nucleotide metabolism.</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":"143968011","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}
Sonali J Bracken, Jonathan C Poe, Stefanie Sarantopoulos
{"title":"What's atypical about human B cells after allogeneic stem cell transplantation?","authors":"Sonali J Bracken, Jonathan C Poe, Stefanie Sarantopoulos","doi":"10.1093/jleuko/qiaf048","DOIUrl":"10.1093/jleuko/qiaf048","url":null,"abstract":"<p><p>Atypical B cells or age-associated B cells represent an alternative lineage of memory B cells. Emerging evidence suggests that context influences the apparent functional heterogeneity of age-associated B cells. While data support a protective role for age-associated B cells in the setting of infection, multiple other studies suggest that these cells play a pathogenic role in the setting of autoimmunity. After treatment with allogeneic hematopoietic stem cell transplantation, the memory B-cell compartment is altered in patients who develop an autoimmune-like syndrome called chronic graft-versus-host disease. Patients with chronic graft-versus-host disease have significantly increased proportions of CD11c+ age-associated B cells within the peripheral compartment that develop under constant exposure to host alloantigens and persist under conditions when B-cell tolerance is not achieved. Herein, we review what is currently known about the molecular alterations in the heterogeneous memory B-cell compartment of hematopoietic stem cell transplantation patients, especially patients with chronic graft-versus-host disease who have developed autoimmune manifestations. In this mini-review, we summarize intrinsic factors in age-associated B cells found in autoimmune states that likely influence their extrafollicular localization, differentiation potential into autoantibody-secreting cells, and function. We highlight lessons from B-cell studies in chronic graft-versus-host disease to provide unique insights into the molecular underpinnings of the diverse functions of age-associated B cells.</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/PMC12089796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010272","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}
Nina Anzic, Walter Stoiber, Astrid Obermeyer, Kirsten D Mertz, Anna Stalder, Jasmin D Haslbauer, Alexandar Tzankov
{"title":"Two-sided effects of neutrophil extracellular traps and changes in the myeloid compartment in acute COVID-19: A histopathological study on autopsy cases from the first and second COVID-19 waves in Switzerland.","authors":"Nina Anzic, Walter Stoiber, Astrid Obermeyer, Kirsten D Mertz, Anna Stalder, Jasmin D Haslbauer, Alexandar Tzankov","doi":"10.1093/jleuko/qiaf056","DOIUrl":"10.1093/jleuko/qiaf056","url":null,"abstract":"<p><p>Severe COVID-19 is characterized by complex immunopathology that involves inflammation, endothelial dysfunction, and immunothrombosis. Neutrophil extracellular traps (NETs) have been recognized as key factors in the severity of the disease, with their emergence correlating to viral load, immmunothrombosis, and organ damage. In this study, we investigated the role of NETosis and macrophage activation in the course of severe COVID-19. We analyzed 23 autopsy samples from patients who died from COVID-19 and performed immunohistochemical staining and stereological point counting to quantify leukocyte infiltration and NET formation among other histopathological parameters. Our results showcase 2 evident immunophenotypes: lowNET and highNET. The lowNET group displayed lower NET formation, higher viral loads, and an increased incidence of secondary infections, as well as shorter survival times. In contrast, the highNET group exhibited increased neutrophil activation, pronounced endothelial damage and thrombotic complications, as well as prolonged survival times. Our data suggest a dual role of NETosis in COVID-19: initially protective, limiting viral replication, but later likely detrimental through immunothrombosis and tissue damage. These findings underline the need for tailored therapeutic actions, with early antiviral and immune-modulating interventions for lowNET patients and strategies aiming to limit excessive NETosis and coagulopathy in highNET patients. Further research is needed to define the timing of interventions based on the dynamics of NETosis.</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":"143986030","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":"Utility of the neutrophil-to-lymphocyte ratio and the ratio of neutrophil-to-lymphocyte ratio after and before adverse events for differential diagnosis of immune-related adverse events and bacterial infections in cancer patients treated with PD-(L)1 inhibitors.","authors":"Lu Han, Beibei Huang, Linlin Li, Benling Xu, Yonghao Yang, Lingdi Zhao, Zibing Wang, Chaoji Zhang, Quanli Gao","doi":"10.1093/jleuko/qiaf029","DOIUrl":"10.1093/jleuko/qiaf029","url":null,"abstract":"<p><p>Differential diagnosis of immune-related adverse events (irAEs) or bacterial infections is sometimes very difficult in cancer patients undergoing treatment with PD-(L)1 inhibitors. This study aimed to assess the effectiveness of the neutrophil-to-lymphocyte ratio (NLR) in distinguishing between irAEs and bacterial infections in cancer patients receiving PD-(L)1 inhibitors. We conducted a retrospective analysis of cancer patients who received at least 1 dose of PD-(L)1 inhibitors at Affiliated Cancer Hospital of Zhengzhou University from 2018 to 2023. We compared the changes in peripheral blood cell counts before and after the occurrence of adverse events, as well as the ratios of the NLR that were closest after the occurrence of adverse events (post-NLR) to the NLR that were closest before the occurrence of adverse events (pre-NLR). Among the 4173 patients who were administered PD-(L)1 inhibitors, 217 individuals experienced a total of 249 irAEs, while 256 patients were diagnosed with 257 bacterial infections. The post-NLR increased significantly compared with pre-NLR in patients with bacterial infection (P < 0.001), while the post-NLR had smaller increase compared with pre-NLR in patients sufffering irAEs (P < 0.001). Notably, the NLR was significantly higher in patients with bacterial infection compared with those with irAEs (P < 0.001). Furthermore, the post-NLR/pre-NLR ratio was higher in the bacterial infection group than in the irAEs group (P < 0.001). The NLR along with the post-NLR/pre-NLR ratio could serve as valuable diagnostic indicators for irAEs and bacterial infections in cancer patients undergoing treatment with PD-(L)1 inhibitors.</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":"143624912","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":"Depletion of natural killer cells enhances wound healing in diabetic mice.","authors":"Jacqueline Cavalcante-Silva, Timothy J Koh","doi":"10.1093/jleuko/qiaf044","DOIUrl":"10.1093/jleuko/qiaf044","url":null,"abstract":"<p><p>Natural killer cells are known for their killing function in infection- and tumor-related responses but also can shape immune responses involved in physiological processes such as wound healing. We recently reported that natural killer cells accumulate in skin wounds and express proinflammatory cytokines that may impede healing. Since impaired wound healing in diabetes is associated with persistent inflammation, the purpose of the present study was to determine whether natural killer cells contribute to impaired skin wound healing in diabetic mice. Here, we show that natural killer cells accumulate at higher levels in wounds in diabetic mice and exhibit less mature phenotypes compared to nondiabetic mice. In addition, local neutralization of CX3CL1 reduced natural killer cell accumulation in wounds of diabetic mice, suggesting that CX3CL1 plays a role in the infiltration of these cells to the wound site. Finally, depletion of natural killer cells in diabetic wounds improved reepithelization and collagen deposition, suggesting that the elevated levels of natural killer cells contribute to impaired healing associated with diabetes.</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/PMC12089793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971577","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}
Zhiyong Zhou, Yi Li, Di Wu, Yiliang Xiao, Shuyan Zeng, Qiuyun Xiao, Siqi Chen, Junpeng Ma, Xin Yuan, Jin Chen, Huiyun Peng
{"title":"Presence of LILRB4 SNP rs1048801 modulates acute myeloid leukemia progression and inhibits CD4+ T cells proliferation.","authors":"Zhiyong Zhou, Yi Li, Di Wu, Yiliang Xiao, Shuyan Zeng, Qiuyun Xiao, Siqi Chen, Junpeng Ma, Xin Yuan, Jin Chen, Huiyun Peng","doi":"10.1093/jleuko/qiaf052","DOIUrl":"10.1093/jleuko/qiaf052","url":null,"abstract":"<p><p>Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4), an emerging immune checkpoint molecule, exhibits therapeutic potential in acute myeloid leukemia (AML). While single nucleotide polymorphisms (SNPs) of immune checkpoint genes have been extensively investigated in AML, the association between LILRB4 genetic polymorphisms and clinical outcomes remains unexplored. We investigated SNPs within the LILRB4 immunoglobulin domain and immunoreceptor tyrosine-based inhibitory motif regions in 151 AML patients and 203 controls. The rs1048801 G allele was significantly associated with increased LILRB4 mRNA expression, higher disease susceptibility, and reduced overall survival. Functional studies revealed that the G allele enhanced AML cell proliferation and colony formation. Furthermore, protein-protein interaction network analysis identified CD4 as a pivotal downstream mediator of LILRB4. Flow cytometry revealed elevated LILRB4 expression in CD45+ leukocytes and CD45+ CD33+ CD14+ monocytic AML cells from G allele carriers, concomitant with reduced CD3+ CD4+ T cell populations and impaired proliferation. Collectively, these findings establish rs1048801 as a critical modulator of AML progression through LILRB4-mediated CD4+ T cell suppression, providing new insights for personalized therapeutic strategies.</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":"144014537","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":"Expanding the role of the chemokine network-the multifaceted role of ACKR2.","authors":"Raffaella Bonecchi, Silvano Sozzani","doi":"10.1093/jleuko/qiaf046","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf046","url":null,"abstract":"","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"117 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101976","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":"Chinese herbal extracts mediated programmed cell death in cancer and inflammation therapy.","authors":"Haihong Yu, Tingmao Xue, Xiaowen Mao","doi":"10.1093/jleuko/qiaf051","DOIUrl":"10.1093/jleuko/qiaf051","url":null,"abstract":"<p><p>Programmed cell death is a common phenomenon in the development of organisms. It is an active and orderly mode of cell death determined by genes. Programmed cell death is usually classified into 3 different types according to the cell morphological changes, stimulus, and biochemical pathways involved, namely, apoptosis, programmed necrosis, and autophagy. Chinese herbal extracts, mainly obtained from traditional Chinese medicine and their primary plants through the physicochemical extraction and separation process, are concentrated with 1 or more effective ingredients from the herbal materials. Recently, studies focused on the influence of traditional Chinese medicine on programmed cell death are increasing, involving the protection of the nervous system and cardio-cerebrovascular system, the prevention of gastrointestinal and immune function damage, the treatment against tumors, and so on. This review mainly focuses on the effects of Chinese herbal extracts on various types of programmed cell death. In addition, the therapeutic approaches and prospects of CHEs are also discussed. Although there are promising clinical applications of Chinese herbal extracts, some challenges are still waiting to be overcome by further research for the wider use of Chinese herbal extracts in clinical practice.</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":"144005808","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}