Journal of Leukocyte Biology最新文献_第4页

Single-cell transcriptome analysis reveals atypical monocytes circulating ahead of acute graft-versus-host disease clinical onset. 单细胞转录组分析揭示了急性移植物抗宿主病临床发病前循环中的非典型单核细胞。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae229

Filipe Martins, Evarist Planet, Denis Marino, Marc Ansari, Didier Trono

{"title":"Single-cell transcriptome analysis reveals atypical monocytes circulating ahead of acute graft-versus-host disease clinical onset.","authors":"Filipe Martins, Evarist Planet, Denis Marino, Marc Ansari, Didier Trono","doi":"10.1093/jleuko/qiae229","DOIUrl":"10.1093/jleuko/qiae229","url":null,"abstract":"Acute graft-versus-host disease (aGVHD) represents the rejection of the recipient's skin, gut, and liver tissues of an allogeneic hematopoietic stem cell transplantation (HSCT) by the donor T cells. The onset of aGVHD is often rapid and its evolution is unpredictable. We undertook the single-cell RNA sequencing of peripheral blood mononuclear cells collected before aGVHD clinical onset in 3 patients and from 1 patient afterward. We used 4 HSCT recipients who remained free of aGVHD as controls. This analysis unveiled the presence of particular subpopulations of circulating monocytes and cytotoxic T cells (CTLs) in pre-aGVHD samples up to 18 d before clinical disease. These pre-aGVHD monocytes were characterized by an upregulation of the M2 polarity marker CD163 and the transmembrane protein SIGLEC1/CD169. At the same time, their CTL counterparts stood out for the upregulation of the CXCL10 receptor CXCR3 and the antigenic stimulation marker CD70. The occurrence of CD163/SIGLEC1 co-expressing monocytes upstream of aGVHD onset was validated using transcriptomic data from an independent cohort and by flow cytometry in additional blood samples. These findings point to potential early diagnostic tools and preventive therapeutic strategies for aGVHD.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467623","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

Macrophage foam cell-derived mediator promotes spontaneous fat lipolysis in atherosclerosis models. 巨噬细胞泡沫细胞衍生介质可促进动脉粥样硬化模型中的自发脂肪溶解。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae210

Dipanjan Banerjee, Debarun Patra, Archana Sinha, Dwaipayan Chakrabarty, Aparup Patra, Raktim Sarmah, Upalabdha Dey, Rajdeep Dutta, Sarada K Bhagabati, Ashis K Mukherjee, Aditya Kumar, Durba Pal, Suman Dasgupta

{"title":"Macrophage foam cell-derived mediator promotes spontaneous fat lipolysis in atherosclerosis models.","authors":"Dipanjan Banerjee, Debarun Patra, Archana Sinha, Dwaipayan Chakrabarty, Aparup Patra, Raktim Sarmah, Upalabdha Dey, Rajdeep Dutta, Sarada K Bhagabati, Ashis K Mukherjee, Aditya Kumar, Durba Pal, Suman Dasgupta","doi":"10.1093/jleuko/qiae210","DOIUrl":"10.1093/jleuko/qiae210","url":null,"abstract":"Ectopic lipid accumulation in macrophages is responsible for the formation of macrophage foam cells (MFCs) which are involved in the crosstalk with the perivascular adipose tissue (PVAT) of the vascular wall that plays a pivotal role in the progression of atherosclerosis. However, the interrelationship between MFCs and PVAT implementing adipocyte dysfunction during atherosclerosis has not yet been established. We hypothesized that MFC-secreted mediator(s) is causally linked with PVAT dysfunction and the succession of atherosclerosis. To test this hypothesis, MFCs were cocultured with adipocytes, or the conditional media of MFCs (MFC-CM) were exposed to adipocytes and found a significant induction of fat lipolysis in adipocytes. The molecular filtration followed by the high-performance liquid chromatography (HPLC) fractionation and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis of MFC-CM revealed a novel mediator fetuin-A (FetA) that significantly augments toll-like receptor 4 (TLR4)-dependent fat lipolysis in adipocytes. Mechanistically, MFC-derived FetA markedly increased TLR4-dependent c-Jun N-terminal kinases (JNK)/extracellular signal-regulated kinases (ERK) activation that causes spontaneous fat lipolysis implementing adipocyte dysfunction. Thus, the present study provides the first evidence of MFC-derived FetA that induces adipocyte dysfunction by the stimulation of spontaneous fat lipolysis. Therefore, targeting the crosstalk between MFCs and adipocytes could be a newer approach to counter the progression of atherosclerosis.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605144","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

Erratum for "Optimizing a 5-factor cocktail to prepare reparative macrophages for wound healing". 为 "优化 5 因子鸡尾酒，为伤口愈合准备修复巨噬细胞 "撰写的勘误。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae238

引用次数: 0

Cxcl10 is protective during mouse-adapted SARS-CoV-2 infection. Cxcl10在小鼠适应性SARS-CoV-2感染期间具有保护作用。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae252

Shamik Majumdar, Joseph D Weaver, Sergio M Pontejo, Mahnaz Minai, Xinping Lu, Ji-Liang Gao, Gibran Holmes, Reed Johnson, Hongwei Zhang, Brian L Kelsall, Joshua M Farber, Derron A Alves, Philip M Murphy

{"title":"Cxcl10 is protective during mouse-adapted SARS-CoV-2 infection.","authors":"Shamik Majumdar, Joseph D Weaver, Sergio M Pontejo, Mahnaz Minai, Xinping Lu, Ji-Liang Gao, Gibran Holmes, Reed Johnson, Hongwei Zhang, Brian L Kelsall, Joshua M Farber, Derron A Alves, Philip M Murphy","doi":"10.1093/jleuko/qiae252","DOIUrl":"10.1093/jleuko/qiae252","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, remains endemic worldwide. Circulating levels of the chemokine CXCL10 are strongly positively associated with poor outcome; however, its precise role in SARS-CoV-2 pathogenesis and its suitability as a therapeutic target have remained undefined. Here, we challenged mice genetically deficient in Cxcl10 with a mouse-adapted strain of SARS-CoV-2. Infected male, but not female, Cxcl10-/- mice displayed increased mortality compared to wild type controls. Histopathological damage, inflammatory gene induction, and virus load in the lungs of male mice were not broadly influenced by Cxcl10 deficiency. However, accumulation of B and T lymphocytes in the lung parenchyma of infected mice was reduced in the absence of Cxcl10. Thus, during acute SARS-CoV-2 infection, Cxcl10 regulates lymphocyte infiltration in lung and confers protection against mortality. Our preclinical model results do not support targeting CXCL10 therapeutically in severe COVID-19.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750949","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

Eosinophil-airway epithelial cell crosstalk reveals the eosinophil-mediated DUOX1 upregulation in a murine allergic inflammation setting. 嗜酸性粒细胞-气道上皮细胞串扰揭示了在小鼠过敏性炎症环境中嗜酸性粒细胞介导的 DUOX1 上调。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae232

Carla Raggi, Francesca Spadaro, Fabrizio Mattei, Adriana Rosa Gambardella, Francesco Noto, Sara Andreone, Michele Signore, Giovanna Schiavoni, Isabella Parolini, Claudia Afferni

{"title":"Eosinophil-airway epithelial cell crosstalk reveals the eosinophil-mediated DUOX1 upregulation in a murine allergic inflammation setting.","authors":"Carla Raggi, Francesca Spadaro, Fabrizio Mattei, Adriana Rosa Gambardella, Francesco Noto, Sara Andreone, Michele Signore, Giovanna Schiavoni, Isabella Parolini, Claudia Afferni","doi":"10.1093/jleuko/qiae232","DOIUrl":"10.1093/jleuko/qiae232","url":null,"abstract":"Blood and airway eosinophilia represent markers for the endotype-driven treatment of allergic asthma. Little is known on mechanisms that link eosinophils and airway epithelial cells before and after these cells are infiltrated by eosinophils during allergic response. Given that innate immune mechanisms, mainly mediated by epithelial-derived cytokines (interleukin [IL]-33, IL-25, TSLP [thymic stromal lymphopoietin]), induce eosinophil-maturing/attractive substances, we thought to evaluate the crosstalk between eosinophils and airway epithelial cells in the context of IL-33-mediated allergic inflammation. DUOX1 was previously described in clinically relevant aspects of allergic inflammation in a HDM -induced allergic asthma mice model, and in patients with chronic sinusitis or allergic asthma. Thus, we evaluated the involvement of HDM and eosinophils in the regulation of DUOX1 in airway epithelial cells. To recapitulate the lung environment present at the allergen challenge time in acute asthma, we set up an in vitro model based on murine bone marrow-derived eosinophils differentiated with IL-5 and then activated with IL-33 (EOs33) and TC1 or C57 airway epithelial cells. We found that treatment of epithelial cells with HDM induced an eosinophil-attractive environment and increased DUOX1 expression. Importantly, we found that the coculture of airway epithelial cells with EOs33 or with conditioned medium from EOs33 enhanced the expression of DUOX1, which was further increased by combined stimulation (HDM plus EOs33). Our results suggest that lung recruited eosinophils once activated by IL-33 could be involved in a crosstalk loop with airway epithelial cells by DUOX1-mediated IL-33 secretion.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502161","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

Neutrophil extracellular traps: potential thrombotic markers and therapeutic targets in colorectal cancer. 中性粒细胞胞外陷阱：结直肠癌的潜在血栓标志物和治疗靶点。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae235

Xianye Huang, Rongquan He, Yanfeng Jiang, Jing Tang, Xiaoyu Xu, Shixue Laoguo, Gang Chen, Jie Ma

{"title":"Neutrophil extracellular traps: potential thrombotic markers and therapeutic targets in colorectal cancer.","authors":"Xianye Huang, Rongquan He, Yanfeng Jiang, Jing Tang, Xiaoyu Xu, Shixue Laoguo, Gang Chen, Jie Ma","doi":"10.1093/jleuko/qiae235","DOIUrl":"10.1093/jleuko/qiae235","url":null,"abstract":"Neutrophil extracellular traps (NETs) are promising promoters in venous thromboembolism (VTE). In the present study, we have investigated the potential thrombogenic role of NETs in colorectal cancer (CRC). A total of 583 patients with gastrointestinal malignancies who were diagnosed with or without VTE by extremities arteriovenous ultrasound and computed tomography were enrolled. The incidence of VTE in CRC was as high as 17.53%. In serological ELISA experiments, Cit-H3, myeloperoxidase, and cfDNA were significantly overexpressed in CRC patients with VTE compared with CRC patients without VTE and healthy individuals. Neutrophils from CRC patients with VTE produced appreciable amounts of NETs after stimulation with phorbol-12-myristate-13-acetate, which were lacking in CRC patients without VTE and healthy individuals. CfDNA was positively correlated with plasmin-α2-antiplasmin complex and tissue plasmin activator inhibitor-1 complex, and Cit-H3 was positively correlated with plasmin-α2-antiplasmin complex, suggesting that NETs are associated with increased fibrinolytic activity. We screened some NETs-related genes by analyzing several high-throughput sequencing datasets of VTE and NETs. FCGR1A was identified as the optimal target gene by pan-cancer expression analysis and survival analysis. FCGR1A was significantly overexpressed in the peripheral blood of CRC patients without VTE compared with healthy individuals and showed a positive correlation with cfDNA. Neutrophil-derived NETs were significantly reduced by FCGR1A inhibitor exposure. These findings indicate that NETs are actively involved in VTE in CRC. NETs are promising thrombotic marker and therapeutic target in CRC to prevent the thrombotic consequences of cancer.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502162","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

CCR2+ monocytes are dispensable to resolve acute pulmonary Pseudomonas aeruginosa infections in WT and cystic fibrosis mice. CCR2+ 单核细胞对解决 WT 小鼠和囊性纤维化小鼠的急性肺铜绿假单胞菌感染是不可或缺的。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae218

Hasan H Öz, Cassia L Braga, Ravindra Gudneppanavar, Caterina Di Pietro, Pamela H Huang, Ping-Xia Zhang, Diane S Krause, Marie E Egan, Thomas S Murray, Emanuela M Bruscia

{"title":"CCR2+ monocytes are dispensable to resolve acute pulmonary Pseudomonas aeruginosa infections in WT and cystic fibrosis mice.","authors":"Hasan H Öz, Cassia L Braga, Ravindra Gudneppanavar, Caterina Di Pietro, Pamela H Huang, Ping-Xia Zhang, Diane S Krause, Marie E Egan, Thomas S Murray, Emanuela M Bruscia","doi":"10.1093/jleuko/qiae218","DOIUrl":"10.1093/jleuko/qiae218","url":null,"abstract":"Extravasation of CCR2-positive monocytes into tissue and to the site of injury is a fundamental immunological response to infections. Nevertheless, exuberant recruitment and/or activity of these monocytes and monocyte-derived macrophages can propagate tissue damage, especially in chronic inflammatory disease conditions. We have previously shown that inhibiting the recruitment of CCR2-positive monocytes ameliorates lung tissue damage caused by chronic neutrophilic inflammation in cystic fibrosis mouse models. A potential concern with targeting monocyte recruitment for therapeutic benefit in cystic fibrosis, however, is whether they are essential for eradicating infections such as Pseudomonas aeruginosa, a pathogen that commonly colonizes and damages the lungs of patients with cystic fibrosis. In this study, we investigated the role of CCR2-positive monocytes in the immune response to acute pulmonary P. aeruginosa infection. Our data show that the altered host immune response caused by the lack of monocyte recruitment to the lungs does not impact P. aeruginosa lung colonization, clearance, and the severity of the infection. These results also hold up in a cystic fibrosis mouse background, which has a hyperinflammatory immune response yet exhibits reduced bactericidal activity. Thus, we lay the groundwork for future studies to investigate the use of CCR2 inhibitors as a potential therapy to ameliorate lung tissue damage in cystic fibrosis. This could be given alone or as an adjunct therapy with CFTR modulators that significantly improve clinical outcomes for eligible patients but do not completely resolve the persistent infection and inflammation that drive lung tissue damage.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372058","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

Role of the basic leucine zipper transcription factor BATF2 in modulating immune responses and inflammation in health and disease. 碱性亮氨酸拉链转录因子 BATF2 在调节健康和疾病中的免疫反应和炎症中的作用。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae245

Rick van der Geest, Janet S Lee

{"title":"Role of the basic leucine zipper transcription factor BATF2 in modulating immune responses and inflammation in health and disease.","authors":"Rick van der Geest, Janet S Lee","doi":"10.1093/jleuko/qiae245","DOIUrl":"10.1093/jleuko/qiae245","url":null,"abstract":"BATF2 is a transcription factor known to exhibit tumor-suppressive activity in cancer cells. Within recent years, however, BATF2 has also emerged as an important transcriptional regulator of the immune system. Through its immunomodulatory function, BATF2 has been implicated in a variety of (patho)physiological processes, including host defense against infection, antitumor immunity, and maintenance of tissue inflammatory homeostasis. Below, we discuss recent literature that has provided insight into the role of BATF2 as a transcriptional regulator of immune responses in health and disease, including the cell types that express BATF2, the different diseases in which the immunomodulatory effects of BATF2 have been shown to play a role, and the molecular mechanisms through which BATF2 is thought to exert those effects. In doing so, we highlight that the immunological effects of BATF2 are highly context dependent, and we point out the overlap between the mechanisms of action of BATF2 in infectious and noninfectious diseases. We also discuss areas of interest for future research, the clinical relevance of better understanding BATF2 function, and potential strategies for therapeutic modulation of BATF2.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590878","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

Cannabinoid receptor type 2 agonist GP1a attenuates macrophage activation induced by M. bovis-BCG by inhibiting NF-κB signaling. 大麻素受体2型激动剂GP1a通过抑制NF-ĸB信号传导来减轻牛乳杆菌-BCG诱导的巨噬细胞活化。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae246

Jessica Do Prado Valeriano, Magaiver Andrade-Silva, Filipe Pereira-Dutra, Leonardo Noboru Seito, Patricia Torres Bozza, Elaine Cruz Rosas, Maria Fernanda Souza Costa, Maria G Henriques

{"title":"Cannabinoid receptor type 2 agonist GP1a attenuates macrophage activation induced by M. bovis-BCG by inhibiting NF-κB signaling.","authors":"Jessica Do Prado Valeriano, Magaiver Andrade-Silva, Filipe Pereira-Dutra, Leonardo Noboru Seito, Patricia Torres Bozza, Elaine Cruz Rosas, Maria Fernanda Souza Costa, Maria G Henriques","doi":"10.1093/jleuko/qiae246","DOIUrl":"10.1093/jleuko/qiae246","url":null,"abstract":"Tuberculosis (TB) is one of the leading causes of death worldwide and a major public health problem. Immune evasion mechanisms and antibiotic resistance highlight the need to better understand this disease and explore alternative treatment approaches. Mycobacterial infection modulates the macrophage response and metabolism to persist and proliferate inside the cell. Cannabinoid receptor type 2 (CB2) is expressed mainly in leukocytes and modulates the course of inflammatory diseases. Therefore, our study aimed to evaluate the effects of the CB2-selective agonist GP1a on irradiated Mycobacterium bovis-BCG (iBCG)-induced J774A.1 macrophage activation. We observed increased expression of CB2 in macrophages after iBCG stimulation. The pretreatment with CB2-agonists, GP1a, JWH-133, and GW-833972A (10 µM), reduced iBCG-induced TNF-α and IL-6 release by these cells. Moreover, the CB2-antagonist AM630 (200 nM) treatment confirmed the activity of GP1a on CB2 by scale down its effect on cytokine production. GP1a pretreatment (10 µM) also inhibited the iBCG-induced production of inflammatory mediators as prostaglandin (PG)E2 and nitric oxide by macrophages. Additionally, GP1a pretreatment also reduced the transcription of proinflammatory genes (inos, il1b, and cox2) and genes related to lipid metabolism (dgat1, acat1, plin2, atgl, and cd36). Indeed, lipid droplet accumulation was reduced by GP1a treatment, which was partially blockade by AM630 pretreatment. Finally, GP1a pretreatment reduced the activation of the NF-κB signaling pathway. In conclusion, the activation of CB2 by GP1a modulated the macrophage response to iBCG by reducing inflammatory mediator levels and metabolic reprogramming.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621926","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

Transgenic αβ TCR tonic signaling is leukemogenic while strong stimulation is leukemia suppressive. 转基因αβ TCR强直信号具有致白血病性，而强刺激则具有抑制白血病性。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae249

Telmo A Catarino, Ivette Pacheco-Leyva, Marina Baessa, João L Pereira, Nuno R Dos Santos

{"title":"Transgenic αβ TCR tonic signaling is leukemogenic while strong stimulation is leukemia suppressive.","authors":"Telmo A Catarino, Ivette Pacheco-Leyva, Marina Baessa, João L Pereira, Nuno R Dos Santos","doi":"10.1093/jleuko/qiae249","DOIUrl":"10.1093/jleuko/qiae249","url":null,"abstract":"The pre-T cell receptor (TCR) and TCR complexes are frequently expressed in T cell acute lymphoblastic leukemia (T-ALL), an aggressive T cell precursor malignancy. Although mutations in TCR components are infrequent in T-ALL, earlier research indicated that transgenic αβ TCR expression in mouse T cell precursors promoted T-ALL development. However, we recently found that stimulation of TCR signaling in T-ALL induced leukemic cell apoptosis and suppressed leukemia. Our aim was to elucidate if a given αβ TCR complex has a dual role in leukemogenesis depending on the nature of the stimulus. We demonstrate that transgenic expression of the Marilyn αβ TCR, specific for the H-Y male antigen presented by major histocompatibility complex class II, triggers T-ALL development exclusively in female mice. This T-ALL exhibited Notch1 mutations, Cdkn2a copy number loss, and immature immunophenotype, and infiltrated both lymphoid and nonlymphoid organs. Furthermore, leukemic cells expressed surface CD5, a marker of tonic TCR signaling. T-ALL efficiently developed in Rag2-deficient Marilyn transgenic females, indicating that Rag2-mediated recombination is not implicated in this T-ALL model. T-ALL development was also observed in the OT-I TCR transgenic mouse model, but it did not occur when major histocompatibility complex class I was abrogated through genetic inactivation of β2-microglobulin. Remarkably, exposure of Marilyn female T-ALL cells to endogenous agonist antigens in male recipient mice or exogenous peptides in female recipient mice resulted in T-ALL apoptosis and prolonged mouse survival. These findings underscore the dual role of the same αβ TCR complex in T-ALL, in which tonic stimulation is leukemogenic, while strong stimulation suppresses leukemia.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687140","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