Journal of Leukocyte Biology最新文献_第4页

Mapping murine thymic epithelial cells: functional ultrastructure and implications for thymopoiesis. 小鼠胸腺上皮细胞定位：功能超微结构及其对胸腺生成的影响。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-08-05 DOI: 10.1093/jleuko/qiaf115

Stepan Vodopyanov, Leslie Gunther-Cummins, Joseph Churaman, Xheni Nishku, Theofilos Poutahidis, Alexandros Hardas, Frank P Macaluso, George S Karagiannis

{"title":"Mapping murine thymic epithelial cells: functional ultrastructure and implications for thymopoiesis.","authors":"Stepan Vodopyanov, Leslie Gunther-Cummins, Joseph Churaman, Xheni Nishku, Theofilos Poutahidis, Alexandros Hardas, Frank P Macaluso, George S Karagiannis","doi":"10.1093/jleuko/qiaf115","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf115","url":null,"abstract":"We present a novel classification system for murine thymic epithelial cells (TECs), identifying 11 distinct types, four in the thymic cortex and seven in the medulla, based on their spatial localization and unique ultrastructural features. As key stromal components of the thymic microenvironment, TECs play indispensable roles in T cell development, including thymocyte selection, antigen presentation, and structural support. Our classification spans from the subcapsular cortex to the deep medulla and incorporates microanatomical context, morphology, and functional characteristics, providing a comprehensive and flexible framework to study TEC heterogeneity in relation to thymopoiesis. Aligning with TEC classification in rats and humans, this system highlights conserved spatial organization across species while remaining adaptable for refinement. Each TEC type is distinguished by features such as chromatin organization, cytoplasmic morphology, vacuolar content, and organelle distribution, attributes that suggest distinct functional contributions to various stages of thymocyte maturation. Importantly, the classification is designed for logical expansion both horizontally (inclusion of additional subtypes within the proposed TEC types) and vertically (inclusion of entirely novel TEC types). By integrating detailed morphological observations with testable functional hypotheses, this framework underscores the essential role of TEC diversity in supporting thymic architecture and orchestrating effective T cell output. Overall, it offers a robust foundation for future research into immune development and the pathological consequences of thymic dysfunction.","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":"144957379","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

Platelets drive macrophage inflammatory activation in vitro. 血小板驱动巨噬细胞体外炎症激活。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-08-05 DOI: 10.1093/jleuko/qiaf114

Anna Rizakou, Annabelle Rosa, Lukas Johannes Weiss, Ecem T Sakalli, Giuseppe Rizzo, Philipp Burkard, Panagiota Arampatzi, Sarah Beck, Shanice Gundel, Kimberly Klapproth, Sourish Reddy Bandi, Marie Piollet, Vanessa Göb, Harald Schulze, David Stegner, Alma Zernecke, Bernhard Nieswandt, Clement Cochain

{"title":"Platelets drive macrophage inflammatory activation in vitro.","authors":"Anna Rizakou, Annabelle Rosa, Lukas Johannes Weiss, Ecem T Sakalli, Giuseppe Rizzo, Philipp Burkard, Panagiota Arampatzi, Sarah Beck, Shanice Gundel, Kimberly Klapproth, Sourish Reddy Bandi, Marie Piollet, Vanessa Göb, Harald Schulze, David Stegner, Alma Zernecke, Bernhard Nieswandt, Clement Cochain","doi":"10.1093/jleuko/qiaf114","DOIUrl":"10.1093/jleuko/qiaf114","url":null,"abstract":"Macrophages have a dual role in tissue healing after injury as they perform tissue repair functions but can also precipitate tissue damage or promote fibrosis. Platelets, beyond their role in thrombosis and hemostasis, are crucial mediators of inflammation and interact with macrophages. Platelet-macrophage interactions have been proposed to modulate macrophage phenotype, including their profibrotic functions, but the full extent of the platelet impact on the macrophage transcriptome is unknown. Here, we aimed to investigate how platelets affect macrophage activation in vitro. Using experimental myocardial infarction (MI) in mice as a model of sterile tissue injury, we readily visualized the direct interaction of platelets with macrophages in the ischemic heart using fluorescence microscopy. Bulk RNA-sequencing of mouse bone marrow-derived macrophages co-cultured in vitro with thrombin-activated platelets showed a widespread proinflammatory activation, with upregulation of genes associated with inflammation (Il1b, Trem1, Tlr2, Cd14), angiogenesis (Vegfa) and response to hypoxia (Hif1a). Resting platelets also led to activation of inflammatory gene expression by macrophages, albeit to a much lesser extent. Activated or resting platelets, or the platelet-derived chemokine CXCL4, had a limited impact on macrophage expression of profibrotic genes (Spp1, Fn1). Using a transwell assay, we further demonstrate that the proinflammatory effects of platelets on the macrophage transcriptome were largely contact dependent. Altogether, our work shows that platelets interact with macrophages in the ischemic heart and polarize macrophages towards a proinflammatory phenotype in vitro, with potential implications for cardiac macrophage inflammatory activation after acute experimental MI.","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":"144835314","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

Causal relationships between immunophenotypes, plasma metabolites, and pancreatic cancer: a mediation Mendelian randomization study. 免疫表型、血浆代谢物和胰腺癌之间的因果关系：一项孟德尔随机研究。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-08-05 DOI: 10.1093/jleuko/qiaf120

Jiawei Liu, Jian Zhou, Hongyu Bie, Xin Li, Cihui Yan, Xiubao Ren

{"title":"Causal relationships between immunophenotypes, plasma metabolites, and pancreatic cancer: a mediation Mendelian randomization study.","authors":"Jiawei Liu, Jian Zhou, Hongyu Bie, Xin Li, Cihui Yan, Xiubao Ren","doi":"10.1093/jleuko/qiaf120","DOIUrl":"10.1093/jleuko/qiaf120","url":null,"abstract":"Existing studies examining the relationships among immunological cell phenotype, plasma metabolites, and pancreatic cancer susceptibility are limited. More comprehensive research is required to elucidate the complex interactions underlying these associations. Genetic instruments for 731 immune phenotypes (N = 3,757), 1,400 circulating metabolites (N = 8,299), and pancreatic cancer (N = 1,196) were derived from a genome-wide association study (GWAS) meta-analysis. A two-step, two-sample Mendelian randomization (MR) study using the Inverse Variance Weighted method was conducted to investigate the causal influence of immune cell phenotypes on pancreatic cancer and to assess the intermediary role of circulating metabolites. Sensitivity analyses were carried out to verify the robustness, potential heterogeneity, and pleiotropy. MR analyses identified protective effects of CD64 on monocyte (OR = 0.859, 95%CI: 0.802 to 0.920, P = 1.65 × 10-5, PBonferroni = 0.012) against pancreatic cancer. Moreover, 68 metabolites were suggestively associated with pancreatic cancer. Notably, mediation MR revealed that the causal role of CD64 on monocytes in pancreatic cancer was largely mediated by 1-palmitoleoylglycerol (16:1) level (OR = 0.0089, 95%CI: 0.00121 to 0.0167, P = 0.023), accounting for 5.91% of the total effect. These findings establish a causal relationship between CD64 on monocytes and pancreatic cancer, possibly operating through circulating metabolites. The research advances knowledge of the interplay between immune responses and the risk of pancreatic cancer, providing important implications for immunologically targeted treatment approaches.","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":"144855518","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

Posttranslational sialylation and its impact on neutrophil recruitment. 翻译后唾液化及其对中性粒细胞募集的影响。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-08-05 DOI: 10.1093/jleuko/qiaf113

Katrin Nussbaumer, Jamey D Marth, Markus Sperandio

{"title":"Posttranslational sialylation and its impact on neutrophil recruitment.","authors":"Katrin Nussbaumer, Jamey D Marth, Markus Sperandio","doi":"10.1093/jleuko/qiaf113","DOIUrl":"10.1093/jleuko/qiaf113","url":null,"abstract":"Neutrophils are essential components of the innate immune system, playing a critical role in responding to infections and inflammation. Their recruitment from blood circulation to affected tissues follows a well-coordinated multistep adhesion and activation cascade. Recent studies highlight the importance of posttranslational modifications, particularly sialylation, in regulating neutrophil recruitment. Sialic acids, negatively charged monosaccharides, are attached to glycoproteins and glycolipids on neutrophil surfaces, influencing their stability, signaling, and interactions with endothelial cells. Selectins, key mediators of neutrophil rolling, recognize sialylated ligands such as sialyl Lewis-X on the neutrophil surface enabling the initial capture and rolling process. Additionally, sialylation of chemokine receptors and integrins modulate neutrophil activation and firm adhesion. Beyond recruitment, sialylation affects neutrophil homeostasis, aging, and clearance, as well as their interactions with pathogens and tumor cells. Dysregulation of sialylation has been linked to autoimmune diseases, cancer progression, and infections, making it an interesting target for therapeutic interventions. This review focuses on the functional role of posttranslational sialylation in neutrophil biology, detailing its impact on leukocyte recruitment, immune modulation, and potential therapeutic applications.","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":"144760326","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

An IL-15-modified NKp30×HER2 trispecific NK cell engager enhances NK cell activation and tumor cell killing. il -15修饰的NKp30×HER2三特异性NK细胞接合器增强NK细胞活化和肿瘤细胞杀伤。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-08-05 DOI: 10.1093/jleuko/qiaf107

Yaping Cheng, Quanxiao Li, Yu Kong, Ailing Huang, Zhenlin Yang, Tianlei Ying, Yanling Wu

{"title":"An IL-15-modified NKp30×HER2 trispecific NK cell engager enhances NK cell activation and tumor cell killing.","authors":"Yaping Cheng, Quanxiao Li, Yu Kong, Ailing Huang, Zhenlin Yang, Tianlei Ying, Yanling Wu","doi":"10.1093/jleuko/qiaf107","DOIUrl":"10.1093/jleuko/qiaf107","url":null,"abstract":"Natural killer (NK) cells represent a promising effector population for tumor immunotherapy. Conventional NK cell engagers (NKCEs), primarily targeting CD16a, show efficacy but face limitations due to receptor polymorphisms and off-target toxicity. Here, we report the development and characterization of a novel trispecific NK cell engager (TriKE) simultaneously targeting the activating receptor NKp30 and the tumor-associated antigen HER2, integrated with a modified interleukin-15 (IL-15 N72D) fused to the IL-15Rα sushi domain (IL-15RαSu) to enhance NK cell proliferation and persistence. Protein expression and affinity analyses confirmed the proper formation of the fusion protein with high-affinity binding to NKp30, HER2, and IL-15 receptor components. Flow cytometry demonstrated dose-dependent binding of the TriKE to primary human NK cells and HER2+ tumor cells. Functionally, the TriKE induced significantly greater NK cell activation, as measured by CD69 expression, compared with a bispecific engager lacking IL-15. Importantly, cytotoxicity assays revealed superior NK-mediated killing of HER2+ tumor cells upon prolonged exposure, highlighting the immunostimulatory effect of the IL-15 moiety. These results establish the αNKp30 TriKE as a potent platform to redirect NK cytotoxicity against HER2+ tumors, combining targeted receptor engagement with cytokine-driven activation to enhance NK cell-based cancer immunotherapy.","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":"144690515","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

Hyperoxia-induced oxidative stress enhances TMEM106B to impair ULK1-mediated autophagy via TLR3/JNK signaling. 高氧诱导的氧化应激增强TMEM106B，通过TLR3/JNK信号通路损害ulk1介导的自噬。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-08-05 DOI: 10.1093/jleuko/qiaf112

Maozhu Xu, Xiaodong Jiang, Chang Peng, Jing Jiang, Tingyang Qin, Haiyan Qin, Cheng Zeng, Yuling Cheng, Xing Yuan, Shuqi Wu, Xiangli Li, Xinxing Xie, Songye Yang, Siwei Mo

{"title":"Hyperoxia-induced oxidative stress enhances TMEM106B to impair ULK1-mediated autophagy via TLR3/JNK signaling.","authors":"Maozhu Xu, Xiaodong Jiang, Chang Peng, Jing Jiang, Tingyang Qin, Haiyan Qin, Cheng Zeng, Yuling Cheng, Xing Yuan, Shuqi Wu, Xiangli Li, Xinxing Xie, Songye Yang, Siwei Mo","doi":"10.1093/jleuko/qiaf112","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf112","url":null,"abstract":"Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and is a major health hazard for preterm infants worldwide. Hyperoxia-induced oxidative stress is one of the major risk factors for the development of BPD, and ideas for timely intervention in the development of BPD are urgently needed to understand this mechanism. The transmembrane protein TMEM106B is a key molecule in the regulation of autophagy function. However, its biological function in BPD remains elusive. In this study, we evaluated that TMEM106B expression was significantly elevated in BPD patients compared with healthy patients with an area under the receiver-operating characteristic curve of 0.7122, suggesting that TMEM106B expression may be associated with the development of BPD. We further found that TMEM106B expression levels were significantly elevated in the neonatal rat BPD model compared with healthy control rats. Hyperoxic stimulation promoted macrophage TMEM106B expression. Consistent with these findings, macrophage reactive oxygen species and apoptosis levels were decreased and autophagy was enhanced after TMEM106B silencing. Hyperoxic stimulation resulted in a significant decrease in TMEM106B expression after TLR3-JNK inhibition. Taken together, our results suggest that hyperoxia-induced oxidative stress inhibited macrophage autophagy by enhancing TMEM106B through the TLR3/JNK signaling pathway and elucidated its TMEM106B-ULK1-dependent mechanism. Therefore, our data support further investigation of TMEM106B as a key molecule interfering with BPD development.","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":"144957326","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

Microvesicles derived from activated T cells promote human mast cell migration via the S1P1 receptor. 来源于活化T细胞的微泡通过S1P1受体促进人肥大细胞迁移。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-08-05 DOI: 10.1093/jleuko/qiaf111

Noam Yishay, Yoseph A Mekori, Irit Shefler

{"title":"Microvesicles derived from activated T cells promote human mast cell migration via the S1P1 receptor.","authors":"Noam Yishay, Yoseph A Mekori, Irit Shefler","doi":"10.1093/jleuko/qiaf111","DOIUrl":"10.1093/jleuko/qiaf111","url":null,"abstract":"Morphologic studies show increased mast cell activation during T-cell-mediated inflammation. Previous research demonstrated that microvesicles from activated T cells, but not from resting T cells, stimulate human mast cells via the MAPK pathway, leading to degranulation and cytokine release. This study investigates whether microvesicles derived from activated T cells also promote mast cell migration. Microvesicles were isolated from activated or resting T-cell supernatants, and mast cell migration was measured using a transwell assay. The molecular mechanisms were analyzed with specific inhibitors. Results showed that microvesicles derived from activated T cells significantly enhanced human mast cell chemotaxis, which depended on ERK and p38 phosphorylation but not on PI3 K. In addition, migration was mediated by the S1P1 receptor rather than S1P2 and by sphingosine kinase 1, indicating a role of S1P1 in mast cell migration induced by microvesicles derived from activated T cells. In summary, microvesicles derived from activated T cells act as chemoattractants, guiding mast cells to inflammatory sites where they become activated, highlighting their importance in T-cell-mediated inflammation.","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":"144760325","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

Treponema pallidum lipoprotein TpF1 regulates METTL14-mediated NF-κB signaling pathway to promote macrophage M2 polarization. 梅毒螺旋体脂蛋白TpF1调节mettl14介导的NF-κB信号通路，促进巨噬细胞M2极化。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-08-05 DOI: 10.1093/jleuko/qiaf099

Qian Cao, Xiangping Zhou, Fei Zou, Rong He, Liena He, Jiajun Chen, Yue Li, Ting Cao, Yumeng Li, Xiaopeng Lan, Shuangquan Liu

{"title":"Treponema pallidum lipoprotein TpF1 regulates METTL14-mediated NF-κB signaling pathway to promote macrophage M2 polarization.","authors":"Qian Cao, Xiangping Zhou, Fei Zou, Rong He, Liena He, Jiajun Chen, Yue Li, Ting Cao, Yumeng Li, Xiaopeng Lan, Shuangquan Liu","doi":"10.1093/jleuko/qiaf099","DOIUrl":"10.1093/jleuko/qiaf099","url":null,"abstract":"During Treponema pallidum (T. pallidum) infection, m6A modification negatively regulates inflammatory responses in macrophages. However, whether m6A modification participates in the regulation of macrophage M2 polarization during T. pallidum infection remains unclear. Using THP-1-derived macrophages as a model, this study investigated the mechanism by which T. pallidum lipoprotein TpF1 promotes macrophage M2 polarization and analyzed the effect of TpF1 on m6A modification in macrophages and the regulatory role of methyltransferase-like 14 (METTL14). Results showed that upon TpF1 stimulation, expression of M2 macrophage markers CD206 and PPARγ was significantly increased, and levels of anti-inflammatory factors TGF-β and CCL18 were upregulated at both mRNA and protein levels. In contrast, expression of M1 marker CD80 and pro-inflammatory factors IL-1β and TNF-α was significantly decreased at both mRNA and protein levels, indicating that TpF1 promotes macrophage polarization toward the M2 phenotype. Meanwhile, TpF1 upregulated global m6A levels in macrophages, accompanied by increased expression of m6A methyltransferase METTL14 and reader protein YTHDF2. Knocking down METTL14 with siRNA inhibited TpF1-induced elevation of global m6A levels and macrophage M2 polarization. Mechanistically, TpF1 promoted macrophage M2 polarization by activating the NF-κB pathway, as demonstrated by the inhibitory effect of NF-κB-specific inhibitors on M2 polarization. Further studies revealed that METTL14 knockdown significantly suppressed TpF1-induced NF-κB activation. These findings indicate that T. pallidum lipoprotein TpF1 promotes macrophage M2 polarization via METTL14-mediated regulation of the NF-κB signaling pathway, offering new insights into the immune evasion mechanisms of Treponema pallidum.","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":"144553756","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

Caspase-11 regulates systemic inflammation and cell death in a cell-specific manner after trauma with shock. Caspase-11以细胞特异性的方式调节创伤休克后的全身炎症和细胞死亡。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-08-05 DOI: 10.1093/jleuko/qiaf121

Joud Mulla, Alyssa Gregory, Hong Liao, Bashar Al Matour, Yuzhen Li, Abiha Abdullah, Timothy R Billiar, Melanie J Scott

{"title":"Caspase-11 regulates systemic inflammation and cell death in a cell-specific manner after trauma with shock.","authors":"Joud Mulla, Alyssa Gregory, Hong Liao, Bashar Al Matour, Yuzhen Li, Abiha Abdullah, Timothy R Billiar, Melanie J Scott","doi":"10.1093/jleuko/qiaf121","DOIUrl":"10.1093/jleuko/qiaf121","url":null,"abstract":"Severe trauma releases damage-associated molecular patterns (DAMPs), which activate the immune system via pattern recognition receptors. This triggers inflammatory cascades that can lead to systemic inflammatory response syndrome, immunosuppression, and multiple organ dysfunction syndrome. Pyroptosis is an inflammatory form of cell death mediated by caspase-11 and gasdermin D (GsdmD). In this study, we examined caspase-11's effects on inflammation, tissue damage, and neutrophil infiltration in a model of severe tissue injury. Male C57BL/6J (WT), caspase-11-/-, cell-specific caspase-11-/- mice (endothelial-specific caspase-11-/- [casp11EC-/-]), platelet-specific caspase-11-/- (casp11plt-/-), and hepatocyte-specific caspase-11-/- (casp11HC-/-) mice were subjected to polytrauma, consisting of hemorrhagic shock (25% total blood volume removed), liver crush, and bilateral lower extremity injury. At 6 h post-polytrauma, blood, plasma, and tissues were collected for analysis. Western blot analysis showed caspase-11 and GsdmD cleavage in the lungs and liver in WT mice at 6 h after polytrauma. GsdmD cleavage was found to be caspase-11 dependent. Inflammatory mediators, plasma IL-6 and CXCL-1/KC, were significantly increased in caspase-11-/-, casp11HC-/- and casp11EC-/- mice compared to WT controls or casp11plt-/-. Liver damage (ALT/AST) was similar between groups. Circulating neutrophil counts were decreased in caspase-11-/-, but neutrophils and neutrophil myeloperoxidase levels were increased in caspase-11-/- liver compared with WT after polytrauma. Our study identifies an unexpected and novel anti-inflammatory function for caspase-11 in trauma, through the regulation of neutrophil influx into tissues. Our findings underscore the significance of caspase-11 activation early after polytrauma to moderate trauma-induced inflammation.","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/PMC12394988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859196","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

Tumor-infiltrating CD103+CD8+hnRNPA2B1+ tissue-resident T cells indicate poor prognosis in patients with clear cell renal cell carcinoma. 肿瘤浸润性CD103+CD8+hnRNPA2B1+组织驻留T细胞提示透明细胞肾细胞癌患者预后不良。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-08-05 DOI: 10.1093/jleuko/qiaf084

Yingting Liu, Jiajin Ma, Bin Xu, Yue Wu, Zhaoyu Xing, Heya Qian, Lujun Chen, Xiao Zheng, Jingting Jiang

{"title":"Tumor-infiltrating CD103+CD8+hnRNPA2B1+ tissue-resident T cells indicate poor prognosis in patients with clear cell renal cell carcinoma.","authors":"Yingting Liu, Jiajin Ma, Bin Xu, Yue Wu, Zhaoyu Xing, Heya Qian, Lujun Chen, Xiao Zheng, Jingting Jiang","doi":"10.1093/jleuko/qiaf084","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf084","url":null,"abstract":"Tumor heterogeneity and the complex immune microenvironment make it challenging to identify candidates for immunotherapy using dominant biomarkers. Tumor-infiltrating CD8+T cells, particularly CD103+CD8+ tissue-resident T cells and their specific subsets, are generally linked to better outcomes in many cancers, but their role in renal cancer remains largely unexplored. Here, we report that tumor-infiltrating CD103+CD8+hnRNPA2B1+ tissue-resident T cells can serve as an unfavorable prognostic factor for ccRCC patients and may be related to PD-1 treatment outcomes. We assessed the infiltration of CD103+CD8+T, CD103+CD8+hnRNPA2B1+T and other CD8+T cell subsets in ccRCC using multiplex immunofluorescence staining, and evaluated their links to patient clinicopathological features and prognosis. With published single-cell data from ccRCC patients treated with PD-1 therapy, we studied the expression differences of hnRNPA2B1 in tumor-infiltrating CD8+ T cells between responders and nonresponders. Compared with adjacent normal tissues, the infiltration levels of CD103+CD8+T, CD103+CD8+hnRNPA2B1+T cells, and CD103+CD8+Bhlhe40+T cells in ccRCC tissues were all significantly higher (all P values were <0.01). Moreover, patients with a higher degree of infiltration of these cells had worse overall survival (HR = 0.3490, 95% CI: 0.09338 to 1.304, P = 0.0144). All of them can serve as independent prognostic factors for ccRCC patients (HR = 3.753, 95% CI: 1.317 to 10.693, P = 0.013). Single-cell transcriptomics revealed that tumor-infiltrating CD8+T cells in patients responding to PD-1 antibody treatment had higher hnRNPA2B1 expression compared with nonresponders. In summary, our study indicates that tumor-infiltrating CD103+CD8+hnRNPA2B1+ tissue-resident T cells can serve as predictive factors and indicators for unfavorable prognosis and patient responses to PD-1 treatment outcomes in ccRCC patients.","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":"144957364","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