Journal of Leukocyte Biology最新文献

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Histone HIST1 genes and tumor-infiltrating lymphocytes in a child with γδ T cell acute lymphoblastic leukemia by single-cell sequencing. 组蛋白HIST1基因与γ δ T细胞急性淋巴细胞白血病儿童肿瘤浸润淋巴细胞的单细胞测序
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI: 10.1093/jleuko/qiaf022
Xiao-Hua Luo, Yan Zhu, Xiao-Qin Duan, Wen Peng, Cai-Xia Pei, Li Yang, Qing Li, Min Zhao, Lan Wang
{"title":"Histone HIST1 genes and tumor-infiltrating lymphocytes in a child with γδ T cell acute lymphoblastic leukemia by single-cell sequencing.","authors":"Xiao-Hua Luo, Yan Zhu, Xiao-Qin Duan, Wen Peng, Cai-Xia Pei, Li Yang, Qing Li, Min Zhao, Lan Wang","doi":"10.1093/jleuko/qiaf022","DOIUrl":"10.1093/jleuko/qiaf022","url":null,"abstract":"<p><p>γδ T cell acute lymphoblastic leukemia (γδ T-ALL) represents a rare subset of T-ALL and is correlated with high rates of induction failure, relapse, and increased mortality. γδ T-ALL lacks a biologically informed framework for guiding its classification and treatment strategies. In this report, we detail a case of child with γδ T-ALL who underwent induction chemotherapy and intensification treatment, followed by haploidentical hematopoietic stem cell transplantation. The patient achieved a clinical complete remission and remains minimal residual disease negative with chidamide maintenance post-transplantation. Single-cell RNA sequencing revealed a connection between histone HIST1 genes and γδ T-ALL and identified potential effector functions of γδ T cells in combating this leukemia. This case carries significant implications for managing γδ T-ALL, highlighting the relationship between histone modification patterns and γδ tumor-infiltrating lymphocytes in γδ T-ALL cells for developing novel therapeutic approaches.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458281","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
Early neutrophil responses are potential biomarkers to predict severe COVID-19 in adults. 早期中性粒细胞反应是预测成人严重COVID-19的潜在生物标志物。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-03-20 DOI: 10.1093/jleuko/qiaf035
Ananya Singh, Nurhidayah Binte Mohamed Yazid, Raika Francesca Morales, Keisuke Ejima, Po Ying Chia, Siew Wai Fong, Lisa F P Ng, Laurent Renia, David Chien Lye, Lousia Jin Sun, Seow Yen Tan, Louis Yi Ann Chai, Shirin Kalimuddin, Barnaby Edward Young, Tsin Wen Yeo, Andrew Teo
{"title":"Early neutrophil responses are potential biomarkers to predict severe COVID-19 in adults.","authors":"Ananya Singh, Nurhidayah Binte Mohamed Yazid, Raika Francesca Morales, Keisuke Ejima, Po Ying Chia, Siew Wai Fong, Lisa F P Ng, Laurent Renia, David Chien Lye, Lousia Jin Sun, Seow Yen Tan, Louis Yi Ann Chai, Shirin Kalimuddin, Barnaby Edward Young, Tsin Wen Yeo, Andrew Teo","doi":"10.1093/jleuko/qiaf035","DOIUrl":"10.1093/jleuko/qiaf035","url":null,"abstract":"<p><p>In the early COVID-19 pandemic, the strain on healthcare facilities highlighted the need for reliable biomarkers to predict progression to severe COVID-19. Neutrophils, the most abundant leukocytes in circulation, are early defenders against pathogens. In a Singaporean adult cohort, early neutrophil mediators were assessed for their suitability as prognostic biomarkers of COVID-19 complications. Plasma levels of myeloperoxidase, elastase, soluble urokinase plasminogen activator receptor (suPAR) and soluble suppressor of tumorigenicity 2 (sST2) in 35 non-severe and 14 severe cases were measured twice, 2-7 days apart after hospitalisation. Nineteen controls were included. The levels of MPO, elastase, suPAR and sST2 were significantly higher in patients with severe COVID-19 compared to those with mild and healthy controls. At baseline sampling, MPO and suPAR predicted severe COVID-19 and had AUROCs of 0.76 and 0.87, respectively. MPO and suPAR at cut-off values of 26.41 ng/ml and 3.19 ng/ml, respectively showed approximately 71% sensitivity and 81 - 84% specificity to differentiate severe COVID-19. In contrast, elastase and neutrophil counts were less predictive of severe disease. In adult COVID-19, MPO and suPAR may be reliable prognostic biomarkers of severe disease during acute COVID-19. Further validation of these markers in a larger cohort and in other infectious diseases is warranted.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663526","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
Sex differences in age-related cardiac and splenic S100A9 and NLRP3 expression. 年龄相关性心脏和脾脏S100A9和NLRP3表达的性别差异。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-03-15 DOI: 10.1093/jleuko/qiaf031
Kathleen Pappritz, Isabel Voss, Muhammad El-Shafeey, Sophie Van Linthout
{"title":"Sex differences in age-related cardiac and splenic S100A9 and NLRP3 expression.","authors":"Kathleen Pappritz, Isabel Voss, Muhammad El-Shafeey, Sophie Van Linthout","doi":"10.1093/jleuko/qiaf031","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf031","url":null,"abstract":"<p><p>Age is an important risk factor for cardiovascular diseases (CVD) and associated with a systemic, low-grade inflammation, so called \"inflammaging\". We aimed to investigate the impact of age and sex on the inflammatory markers S100A9 and components of the NLRP3 inflammasome at an early stage in the aging process, using mature adult and middle-aged/perimenopausal mice. Given the importance of the cardiosplenic axis in heart failure, the spleen was analyzed in addition to the left ventricle and cardiac fibroblasts. Using immunohistochemistry, flow cytometry and gene expression analysis, our study demonstrates a higher inflammatory state of the spleen in perimenopausal versus age-matched males and 3-months old female mice, whereas aging is associated with higher left ventricular gene expression of S100A9 and NLRP3 inflammasome components independent of sex. In conclusion, our data indicate that inflammatory signatures in the spleen and left ventricle already differ in middle-aged mice and are partly sex-dependent.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630675","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
Glutamine modulates neutrophil recruitment and effector functions during sterile inflammation. 谷氨酰胺能调节无菌炎症期间中性粒细胞的招募和效应功能。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae243
Katharina E M Hellenthal, Katharina Thomas, Nadine Ludwig, Anika Cappenberg, Lena Schemmelmann, Tobias Tekath, Andreas Margraf, Sina Mersmann, Katharina Henke, Jan Rossaint, Alexander Zarbock, Wida Amini
{"title":"Glutamine modulates neutrophil recruitment and effector functions during sterile inflammation.","authors":"Katharina E M Hellenthal, Katharina Thomas, Nadine Ludwig, Anika Cappenberg, Lena Schemmelmann, Tobias Tekath, Andreas Margraf, Sina Mersmann, Katharina Henke, Jan Rossaint, Alexander Zarbock, Wida Amini","doi":"10.1093/jleuko/qiae243","DOIUrl":"10.1093/jleuko/qiae243","url":null,"abstract":"<p><p>During sterile inflammation, tissue damage induces excessive activation and infiltration of neutrophils into tissues, where they critically contribute to organ dysfunction. Tight regulation of neutrophil migration and their effector functions is crucial to prevent overshooting immune responses. Neutrophils utilize more glutamine, the most abundant free α-amino acid in the human blood, than other leukocytes. However, under inflammatory conditions, the body's requirements exceed its ability to produce sufficient amounts of glutamine. This study investigates the impact of glutamine on neutrophil recruitment and their key effector functions. Glutamine treatment effectively reduced neutrophil activation by modulating β2-integrin activity and chemotaxis in vitro. In a murine in vivo model of sterile inflammation induced by renal ischemia-reperfusion injury, glutamine administration significantly attenuated neutrophil recruitment into injured kidneys. Transcriptomic analysis revealed, glutamine induces transcriptomic reprograming in murine neutrophils, thus improving mitochondrial functionality and glutathione metabolism. Further, glutamine influenced key neutrophil effector functions, leading to decreased production of reactive oxygen species and formation of neutrophil extracellular traps. Mechanistically, we used a transglutaminase 2 inhibitor to identify transglutaminase 2 as a downstream mediator of glutamine effects on neutrophils. In conclusion, our findings suggest that glutamine diminishes activation and recruitment of neutrophils and thus identify glutamine as a potent means to curb overshooting neutrophil responses during sterile inflammation.</p>","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":"142590871","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
MerTK signaling in human primary T cells modulates memory potential and improves recall response. 人原代 T 细胞中的 MerTK 信号调节记忆潜能并改善回忆反应
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae226
Anne Rahbech, Annina Kurzay, Sara Fresnillo Saló, Tina Seremet, Reno Debets, Özcan Met, Marlies J W Peeters, Per Thor Straten
{"title":"MerTK signaling in human primary T cells modulates memory potential and improves recall response.","authors":"Anne Rahbech, Annina Kurzay, Sara Fresnillo Saló, Tina Seremet, Reno Debets, Özcan Met, Marlies J W Peeters, Per Thor Straten","doi":"10.1093/jleuko/qiae226","DOIUrl":"10.1093/jleuko/qiae226","url":null,"abstract":"<p><p>Immune therapy using checkpoint inhibitors or adoptive cell transfer has revolutionized the treatment of several types of cancers. However, response to treatment is currently limited to a fraction of patients. Elucidation of immune modulatory mechanisms might optimize patient selection and present ways to modify anti-cancer immune responses. We recently discovered the expression and an important costimulatory role of TAM receptor MerTK signaling on activated human primary CD8+ T cells. Here we extend our study of the costimulatory role of MerTK expression in human CD8+ T cells. We uncover a clear link between MerTK expression and less differentiated Central Memory T cells based on an increased expression of CCR7, CD45RO, CD28, CD62L, and an altered metabolic profile. In addition, we observe an improved proliferative capacity and elevated expression of effector molecule IFNγ upon recall responses of MerTK-expressing cells in vitro. Finally, using gp100TCR-transduced T cells, we demonstrate how PROS1 treatment results in improved cytotoxicity and killing of tumors. Our findings describe a role of MerTK expression in T cells, which could be exploited in the search for improving immunotherapeutic approaches.</p>","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":"142467621","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
Chemerin in immunity. 免疫中的 Chemerin
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae181
Mattia Laffranchi, Tiziana Schioppa, Francesca Sozio, Arianna Piserà, Laura Tiberio, Valentina Salvi, Daniela Bosisio, Tiziana Musso, Silvano Sozzani, Annalisa Del Prete
{"title":"Chemerin in immunity.","authors":"Mattia Laffranchi, Tiziana Schioppa, Francesca Sozio, Arianna Piserà, Laura Tiberio, Valentina Salvi, Daniela Bosisio, Tiziana Musso, Silvano Sozzani, Annalisa Del Prete","doi":"10.1093/jleuko/qiae181","DOIUrl":"10.1093/jleuko/qiae181","url":null,"abstract":"<p><p>Chemerin is a distant member of the cystatin protein family, initially discovered as a chemotactic factor and subsequently also reported to act as adipokine and angiogenetic factor. The biological activity of chemerin is regulated at different levels, such as gene expression, protein processing, and interaction with both signaling and nonsignaling receptors. Chemerin is mostly produced by stromal cells, such as adipocytes, fibroblasts, and epithelial and endothelial cells, and circulates in almost all human tissues as a zymogen that needs to be proteolytically activated to exert its biological functions. At the receptor level, chemerin binds a G protein-coupled 7-transmembrane domain receptor Chemerin1 (also named ChemR23 and CMKLR1), mostly expressed by innate immune cells, such as macrophages, dendritic cells, and natural killer cells, and by border cells. In addition, chemerin may bind GPR1, a weak signaling receptor, and CCRL2, a nonsignaling receptor expressed by barrier cells, such as endothelial and epithelial cells, able to regulate leukocytes' migration by multiple mechanisms. The aim of this review is to summarize the contribution of chemerin in the regulation of immune responses.</p>","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":"142125975","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
Polarization of the memory B-cell response. 记忆 B 细胞反应的极化。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae228
Lizzette Pérez-Pérez, Brian J Laidlaw
{"title":"Polarization of the memory B-cell response.","authors":"Lizzette Pérez-Pérez, Brian J Laidlaw","doi":"10.1093/jleuko/qiae228","DOIUrl":"10.1093/jleuko/qiae228","url":null,"abstract":"<p><p>Memory B cells are long-lived cells that are induced following infection or vaccination. Upon antigen re-encounter, memory B cells rapidly differentiate into antibody-secreting or germinal center B cells. While memory B cells are an important component of long-term protective immunity following vaccination, they also contribute to the progression of diseases such as autoimmunity and allergy. Numerous subsets of memory B cells have been identified in mice and humans that possess important phenotypic and functional differences. Here, we review the transcriptional circuitry governing memory B-cell differentiation and function. We then summarize emerging evidence that the inflammatory environment in which memory B cells develop has an important role in shaping their phenotype and examine the pathways regulating the development of memory B cells during a type 1-skewed and type 2-skewed immune response.</p>","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/PMC11953070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467622","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
The tumor-neutrophil interactions in the microenvironment of brain metastases with different primary sites. 不同原发部位脑转移瘤微环境中肿瘤与中性粒细胞的相互作用。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae248
Tamer A Kaya, Klaus-Peter Stein, Anna Schaufler, Belal Neyazi, Ali Rashidi, Ulf D Kahlert, Christian Mawrin, I Erol Sandalcioglu, Claudia A Dumitru
{"title":"The tumor-neutrophil interactions in the microenvironment of brain metastases with different primary sites.","authors":"Tamer A Kaya, Klaus-Peter Stein, Anna Schaufler, Belal Neyazi, Ali Rashidi, Ulf D Kahlert, Christian Mawrin, I Erol Sandalcioglu, Claudia A Dumitru","doi":"10.1093/jleuko/qiae248","DOIUrl":"10.1093/jleuko/qiae248","url":null,"abstract":"<p><p>Brain metastases originating from lung and breast cancer can recruit and activate neutrophils to acquire a tumor-promoting phenotype. It is currently unclear if this phenomenon also occurs in brain metastases arising from other primary sites. Here, we investigated the effect of tumor cells isolated from melanoma, lung cancer, and gastrointestinal cancer brain metastases on neutrophil biology and functions. We found that lung and gastrointestinal but not melanoma brain metastasis cells produced CXCL8/IL-8 and promoted neutrophil recruitment. Similarly, lung and gastrointestinal but not melanoma brain metastasis cells prolonged the survival of neutrophils and stimulated them to release MMP9 and CCL4/MIP1β. In situ, lung and gastrointestinal brain metastasis tissues contained significantly higher numbers of tumor-infiltrating neutrophils compared to melanoma brain metastases. The levels of neutrophil infiltration significantly correlated with the proliferation index of these tumors. Our findings identify variabilities in the immune microenvironment of brain metastases with different primary sites, which may ultimately affect their pathophysiology and progression.</p>","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":"142681884","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
New insights on extramedullary granulopoiesis and neutrophil heterogeneity in the spleen and its importance in disease. 关于髓外粒细胞生成和脾脏中性粒细胞异质性及其在疾病中重要性的新见解。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae220
Rongxia Guo, Xuemei Xie, Qian Ren, Pei Xiong Liew
{"title":"New insights on extramedullary granulopoiesis and neutrophil heterogeneity in the spleen and its importance in disease.","authors":"Rongxia Guo, Xuemei Xie, Qian Ren, Pei Xiong Liew","doi":"10.1093/jleuko/qiae220","DOIUrl":"10.1093/jleuko/qiae220","url":null,"abstract":"<p><p>Neutrophils are traditionally viewed as uncomplicated exterminators that arrive quickly at sites of infection, kill pathogens, and then expire. However, recent studies employing modern transcriptomics coupled with novel imaging modalities have discovered that neutrophils exhibit significant heterogeneity within organs and have complex functional roles ranging from tissue homeostasis to cancer and chronic pathologies. This has revised the view that neutrophils are simplistic butchers, and there has been a resurgent interest in neutrophils. The spleen was described as a granulopoietic organ more than 4 decades ago, and studies indicate that neutrophils are briefly retained in the spleen before returning to circulation after proliferation. Transcriptomic studies have discovered that splenic neutrophils are heterogeneous and distinct compared with those in blood. This suggests that a unique hematopoietic niche exists in the splenic microenvironment, i.e., capable of programming neutrophils in the spleen. During severe systemic inflammation with an increased need of neutrophils, the spleen can adapt by producing neutrophils through emergency granulopoiesis. In this review, we describe the structure and microanatomy of the spleen and examine how cells within the splenic microenvironment help to regulate splenic granulopoiesis. A focus is placed on exploring the increase in splenic granulopoiesis to meet host needs during infection and inflammation. Emerging technologies such as single-cell RNA sequencing, which provide valuable insight into splenic neutrophil development and heterogeneity, are also discussed. Finally, we examine how tumors subvert this natural pathway in the spleen to generate granulocytic suppressor cells to promote tumor growth.</p>","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":"142605145","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
Interleukin-10 inhibits important components of trained immunity in human monocytes. 白细胞介素-10 可抑制人类单核细胞中训练有素的免疫力的重要组成部分。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae240
Rutger J Röring, Flavia Scognamiglio, Lisanne C de Jong, Laszlo A Groh, Vasiliki Matzaraki, Valerie A C M Koeken, Leo A B Joosten, Athanasios Ziogas, Mihai G Netea
{"title":"Interleukin-10 inhibits important components of trained immunity in human monocytes.","authors":"Rutger J Röring, Flavia Scognamiglio, Lisanne C de Jong, Laszlo A Groh, Vasiliki Matzaraki, Valerie A C M Koeken, Leo A B Joosten, Athanasios Ziogas, Mihai G Netea","doi":"10.1093/jleuko/qiae240","DOIUrl":"10.1093/jleuko/qiae240","url":null,"abstract":"<p><p>Trained immunity induces antigen-agnostic enhancement of host defense and protection against secondary infections, but inappropriate activation can contribute to the pathophysiology of inflammatory diseases. Tight regulation of trained immunity is therefore needed to avoid pathology, but little is known about the endogenous processes that modulate it. Here, we investigated the potential of interleukin (IL)-10, a prototypical anti-inflammatory cytokine, to inhibit trained immunity. IL-10 induced tolerance and inhibited trained immunity in primary human monocytes at both functional and transcriptional levels. Inhibition of STAT3, a signaling route that mediates IL-10 signals, induced trained immunity. IL-10 downregulated glycolytic and oxidative metabolism in monocytes but did not impact the metabolic effects of β-glucan-induced trained immunity. Furthermore, IL-10 prevented increased reactive oxygen species production in Bacillus Calmette-Guérin (BCG)-induced training but did not influence phagocytosis upregulation. In a cohort study of healthy volunteers vaccinated with BCG, genetic variants that influenced IL-10 or its receptor modulated BCG-induced trained immunity. Furthermore, circulating IL-10 concentrations were negatively correlated with induction of trained immunity after BCG vaccination in a sex-specific manner. In conclusion, IL-10 inhibited several, albeit not all, immunological functions amplified after induction of trained immunity. Follow-up studies should explore the precise molecular mechanism that mediates the effects of IL-10 on trained immunity. Addressing these knowledge gaps is an important step toward optimizing IL-10's potential as a therapeutic target in diseases characterized by inappropriate induction of trained immunity.</p>","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":"142621940","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
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