Journal of Leukocyte Biology最新文献

{"title":"Secreted cyclophilin A regulates the development of adaptive immune response by modulating B and T cell functional activity in experimental models in vivo and in vitro.","authors":"Anastasiia A Kalinina, Leila R Tilova, Dmitry B Kazansky, Ludmila M Khromykh","doi":"10.1093/jleuko/qiaf089","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf089","url":null,"abstract":"<p><p>Cyclophilin A (CypA) is a member of the isomerase family; in the secreted form, it acts as a chemoattractant and pro-inflammatory factor, orchestrating the development of the local inflammatory response. In this work, we studied the role of secreted CypA in regulating an adaptive immune response. Our findings showed that injections of recombinant human CypA (rhCypA) into mice induced nonspecific activation of T and B cells in vivo that resulted in stimulation of the humoral immune response and suppression of the cellular immune response to model antigens. In vitro, rhCypA-induced activation and proliferation of nonprimed B cells, acted as a co-mitogen for CD40-stimulated B cells and improved their functions as antigen-presenting cells by regulating the expression of CD86 and the major histocompatibility complex (MHC) class II. These immunoregulatory effects of rhCypA could be, at least partially, implemented by modulating the expression of its receptor CD147 on B cells. Having no effects on nonprimed T cells, rhCypA boosted the proliferation of T cells activated through a T cell receptor and enhanced their cytotoxic activity. Here, we proposed secretory CypA as a regulator of the adaptive immune response and provided an insight into CypA-mediated remodeling of T and B cell functional activity.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"117 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835319","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":"Mechanisms of immune suppression in sepsis/shock: one investigator's/lab group's experience (SLB 2024 legacy award presentation).","authors":"Alfred Ayala","doi":"10.1093/jleuko/qiaf108","DOIUrl":"10.1093/jleuko/qiaf108","url":null,"abstract":"<p><p>When I think about scientific/professional \"legacy,\" for me there are at least 3 areas to consider: 1) the actual scientific legacy you (and your lab members) have contributed to, 2) the people you have touched and how they touch you in this scientific journey, and 3) what professional impact you left on the scientific/academic community. So, with that in mind, I will try to share my (our lab groups') story relative to our contributions to the delineation of various mechanisms that appear to contribute to the development of immune suppression and/or organ injury resultant from shock and/or septic insult by weaving in and out of the science over the past ∼35 yr, while digressing from the pure science at certain places in hope of giving you some personal/professional context that effected this individual's (lab groups') scientific journey. Inasmuch, please appreciate that the science discussed will be more of a summary of the contributions we think we may have made (appreciating as possible the contributions of colleagues in the field that spoke to such findings) relative to the understanding of the mechanisms of immune suppression in shock/sepsis and will not be a deep dive into the specific data sets.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698826","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":"Decreased HLA-DR+CD3+ T cells three months after allogeneic stem cell transplantation predict severe chronic GvHD and transplant-related mortality.","authors":"Stefan Koeck, Gabriele Hetzenauer, Ines Peschel-Schaar, Dominik Wolf, Normann Steiner, David Nachbaur","doi":"10.1093/jleuko/qiaf106","DOIUrl":"10.1093/jleuko/qiaf106","url":null,"abstract":"<p><p>Chronic graft vs host disease (cGvHD) is a major late determinant of transplant related mortality (TRM) after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated the predictive value of peripheral blood activated HLA-DR+CD3+ T cells as a novel biomarker. In total, 107 patients were included in this retrospective analysis. Peripheral blood HLA-DR+CD3+ T cells were measured by flow cytometry 3 mo after HSCT. A HLA-DR+CD3+ T cell count <140 cells/µL at month 3 after HSCT correlated significantly with an increased TRM. A HLA-DR+CD3+ T cell count <100 cells/µL was associated with a higher rate of cGvHD grade 2 to 3. Subgroup analyses revealed significant results for TRM and cGvHD grade 2 to 3 for patients with a reduced intensity conditioning. In summary, low HLA-DR+CD3+ T cells in the peripheral blood 3 mo after HSCT may represent a novel biomarker to identify patients with an increased risk for TRM and cGvHD grade 2 to 3.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690516","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 bactericidal and thrombotic potentials of extracellular TRAP-enclosed neutrophil vesicles released in response to Staphylococcus aureus at high glucose concentration.","authors":"Athira S Mohan, Muhamad K Shafi, Merin Mathew, Binchu V Shaji, Sruthi Radhakrishnan, Neethu Mohan, Anie Y","doi":"10.1093/jleuko/qiaf109","DOIUrl":"10.1093/jleuko/qiaf109","url":null,"abstract":"<p><p>The ejection of neutrophil extracellular traps (NETs) is one of the characteristic features of neutrophils. Rapid release of NET-containing extracellular vesicles (NET-EVs) to the extracellular space has been reported as a novel NET release mechanism in response to Staphylococcus aureus. An increased number of these NET-EVs are released from neutrophils maintained at high-glucose conditions. Though NET is released to fight infection, unregulated NET release observed in inflammatory diseases causes thrombosis. This study was planned to analyze the antibacterial and thrombotic potentials of NET-EVs. Freshly isolated human neutrophils were treated with different glucose concentrations along with S. aureus culture supernatant to stimulate NET release. Increased release of NET-EVs was observed from 15 mM glucose concentration onward. Neutrophil origin of these NET-EVs was established using anti-CD63 antibody and the presence of NET components were confirmed. Then, NET-EVs were analyzed for antimicrobial and antibiofilm activities, clotting time, thrombin time, platelet aggregation and fibrinolysis. The NET-EVs possessed both antibacterial and antibiofilm activities, which were diminished in NET-EVs released at higher glucose concentrations. Clotting and platelet aggregation in the presence of NET-EVs were considerably less up to glucose concentrations of 15 and 20 mM, respectively, after which both increased drastically. Fibrinolysis was slower at glucose concentrations higher than 15 mM. In conclusion, NET-EVs shared many characteristics of suicidal NETs such as antibacterial, antibiofilm, and thrombotic properties. The formation of NET-EVs seems to be an adaptation of neutrophils to reduce local inflammation and to extend their antimicrobial activity to distant areas.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835315","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":"γδ T cells in pediatric sepsis.","authors":"Wenjie Zhou, Ting Feng, Liman Li, Zhuoxu He, Yueli Mu, Dong Liu, Hong Li","doi":"10.1093/jleuko/qiaf118","DOIUrl":"10.1093/jleuko/qiaf118","url":null,"abstract":"<p><p>Pediatric sepsis has constantly increased over the world, and is now a leading cause of children's morbidity and mortality. Due to this alarming trend, intense research has been sparked into the unique characteristics of pediatric sepsis, the mechanisms behind the immune dysfunction, and opportunities for improving treatment. Recent findings have underscored the critical role of γδ T cells in the immune response, and their dysfunction has been linked to various diseases, including pediatric sepsis. This review explores γδ T-cell dysfunction in pediatric sepsis, focusing on their impaired activation, proliferation, altered cytokine production, exhaustion, and apoptosis, all of which collectively weaken the immune response in children. The review underscores the significance of γδ T-cell immunology in pediatric sepsis and highlights the notable functional disparities between children and adults. Ongoing research is essential to fully understand the role of γδ T cells in the pathogenesis of sepsis and to develop more effective treatments that will enhance outcomes for affected children.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835318","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":"Microenvironmental conditions and serum availability alter primary human macrophage NF-κB inflammatory response and function.","authors":"Breana Channer, Marzieh Daniali, Lexi Sheldon, Katy Emanuel, Yash Agarwal, Taylor Kist, Brian J Murphy, Meng Niu, Will Dampier, Howard Fox, Peter J Gaskill","doi":"10.1093/jleuko/qiaf071","DOIUrl":"10.1093/jleuko/qiaf071","url":null,"abstract":"<p><p>Macrophages are central to innate immunity and are routinely used in vitro to examine molecular mechanisms contributing to innate immune signaling. However, there is a lack of consensus within the field for optimal in vitro culturing methods, and it is not well understood whether differences in culture conditions produce incongruent outcomes. Here, we compared the effects of commonly used culture medium compositions on TLR4-mediated proinflammatory activity in primary human monocyte-derived macrophages (hMDMs) isolated from healthy blood donors. hMDMs were cultured in fetal bovine serum (FBS)-containing or FBS-free conditions in either Dulbecco's Modified Eagle Medium (DMEM), RPMI, or in Macrophage-Serum Free Medium (M-SFM). Lipopolysaccharide-mediated immune response was measured through nuclear factor κB activation and cytokine and chemokine secretion, which were muted in M-SFM cultures compared with DMEM and RPMI cultures. FBS supplementation increased total cytokine secretion in response to lipopolysaccharide but also showed higher baseline secretion, suggesting a proinflammatory phenotype. Moreover, M-SFM cultures exhibited less phagocytosis compared with DMEM and RPMI cultures. Morphologic analysis of unstimulated hMDMs revealed the highest cell area and length-to-width ratio in M-SFM compared with DMEM or RPMI cultures. FBS-free and M-SFM conditions produced distinct transcriptional profiles compared with media supplemented with FBS, most notably in cell cycle pathways and lipid homeostasis, respectively. Overall, DMEM and RPMI produce comparable morphologic and functional results, albeit with some small differences, while M-SFM produces a muted inflammatory response in macrophages. These data demonstrate that in vitro microenvironment drives differential inflammatory outcomes in human macrophages and is a critical component of experimental design in this cell type.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119631","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":"Downregulation of MicroRNA-93 inhibits proliferation and promotes apoptosis and hematopoiesis in myelodysplastic syndrome cells through PAG1-mediated epidermal growth factor receptor signaling pathway.","authors":"Junyu Liu, Hua Wang, Caihua Zhang","doi":"10.1093/jleuko/qiaf083","DOIUrl":"10.1093/jleuko/qiaf083","url":null,"abstract":"<p><p>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 stem cell factor (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 myelodysplastic syndrome (MDS) and promoting hematopoiesis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-09","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}

{"title":"Potential functions of TRPM2 and TRPM7 channels in the tumor microenvironment.","authors":"Irma Yadira Izaguirre-Hernández, Adriana Sumoza-Toledo","doi":"10.1093/jleuko/qiaf098","DOIUrl":"10.1093/jleuko/qiaf098","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a complex and dynamic ecosystem consisting of both cellular and non-cellular components that collectively modulate the antitumor immune response, as well as cancer growth, invasion, metastasis, immune evasion, and resistance to therapy. Calcium (Ca2+) and magnesium (Mg2+) are two essential ions for a wide range of cellular processes, including proliferation, differentiation, migration, and protein secretion. The intracellular homeostasis and spatiotemporal distribution of these two ions are tightly regulated by ion channels, notably members of the transient receptor potential melastatin (TRPM) subfamily, such as TRPM2 and TRPM7. TRPM2 is a Ca2+-permeable channel activated by ADP-ribose (ADPR) and reactive oxygen species (ROS), whereas TRPM7 permeates both Ca2+ and Mg2+ ions and exhibits constitutive activity. Both channels have been involved in redox-sensitive signaling and function as temperature sensors across various physiological and pathological contexts, such as cancer. Here, we provide an overview of the potential roles of TRPM2 and TRPM7 in regulating cellular dynamics within the TME, with a focus on their contributions to immune modulation.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600707","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":"Remembering Michael P. Cancro: modern Renaissance Man.","authors":"Mary M Tomayko, Jean L Scholz","doi":"10.1093/jleuko/qiaf079","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf079","url":null,"abstract":"","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"117 7","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600708","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":"Human neutrophils are a cellular source of apolipoprotein A-I.","authors":"Xianglan Yao, Joni Mills, Pradeep K Dagur, Wan-Chi Lin, Maria Lopez-Ocasio, Meixia Gao, Zu-Xi Yu, Kazuyo Takeda, Karen J Keeran, Ick Ho Kim, Amisha V Barochia, Stewart J Levine","doi":"10.1093/jleuko/qiaf104","DOIUrl":"10.1093/jleuko/qiaf104","url":null,"abstract":"<p><p>Apolipoprotein A-I (APOA1), the major protein of high-density lipoproteins, has anti-inflammatory functions. APOA1 is primarily produced in the liver; however, it is not known whether neutrophils are a cellular source. Here, we assessed whether human neutrophils express APOA1. Peripheral blood and bronchoalveolar lavage fluid (BALF) were obtained from healthy volunteers (HVs) and asthmatics. Peripheral blood neutrophils from HVs expressed APOA1 at both the mRNA and protein levels, while confocal microscopy demonstrated that APOA1 was localized to a unique population of intracytoplasmic granules. In HVs and asthmatics, APOA1 was preferentially expressed by neutrophils with high side-scatter (SSChigh) in blood and BALF. Furthermore, APOA1+ SSChigh neutrophils were characterized as a population with high levels of caspase-3/caspase-7 activation and CCR5 expression. Since APOA1 has anti-inflammatory functions, this suggests that APOA1 expression by neutrophils may represent a mechanism to attenuate excessive inflammatory responses in health and disease.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626560","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}