Journal of Leukocyte Biology最新文献_第2页

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-09-23 DOI: 10.1093/jleuko/qiaf135

Sophie Reiner, Ethan Reiner, William M Nauseef

引用次数: 0

Harnessing scRNA-seq and bulk RNA-seq to identify CD39+T cell genes for rheumatoid arthritis diagnosis and therapy. 利用scRNA-seq和bulk RNA-seq鉴定CD39+T细胞基因用于类风湿关节炎的诊断和治疗

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-09-17 DOI: 10.1093/jleuko/qiaf130

Dandan Yun, Chenglin Xu, Hongwei Yu, Xintao Liu, Dan Liu

{"title":"Harnessing scRNA-seq and bulk RNA-seq to identify CD39+T cell genes for rheumatoid arthritis diagnosis and therapy.","authors":"Dandan Yun, Chenglin Xu, Hongwei Yu, Xintao Liu, Dan Liu","doi":"10.1093/jleuko/qiaf130","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf130","url":null,"abstract":"Rheumatoid arthritis (RA) is a prevalent autoimmune disorder with an elusive pathogenesis, hindering early detection and therapeutic advancements. This study focuses on CD39+ T cells, which play a significant role in RA, to identify diagnostic and therapeutic biomarkers. We analyzed scRNA-seq data from RA patients to identify differentially expressed genes (DEGs) associated with CD39+ T cells. We then cross-referenced these DEGs with those from normal and RA samples to extract a CD39+ T cell gene signature. Functional enrichment analysis and machine learning algorithms identified key hub genes and assessed their diagnostic efficacy. We identified 13 genes linked to crucial biological pathways, including T cell activation, leukocyte adhesion, and ferroptosis. Four genes, including PELI1, emerged as central to these processes. PELI1 showed remarkable diagnostic value and was upregulated in RA patients. We observed distinct immune cell infiltration patterns based on PELI1 expression and mapped out a lncRNA-miRNA-PELI1 network. We also identified 41 small molecule drugs as potential therapeutic candidates for RA. PELI1 is a promising diagnostic biomarker for RA, contributing to the pool of potential biomarkers for diagnosis and therapy. Our study provides new insights into the role of CD39+ T cells in RA and highlights potential therapeutic targets for future research.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092204","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

Transcriptome-wide Mendelian randomization exploring dynamic CD4+ T cell gene expression in colorectal cancer development. 全转录组孟德尔随机化研究动态CD4+ T细胞基因表达在结直肠癌发展中的作用。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-09-17 DOI: 10.1093/jleuko/qiaf131

Benedita Deslandes, Xueyan Wu, Matthew A Lee, Lucy J Goudswaard, Gareth W Jones, Andrea Gsur, Annika Lindblom, Shuji Ogino, Veronika Vymetalkova, Alicja Wolk, Anna H Wu, Jeroen R Huyghe, Ulrike Peters, Amanda I Phipps, Claire E Thomas, Rish K Pai, Robert C Grant, Daniel D Buchanan, James Yarmolinsky, Marc J Gunter, Jie Zheng, Emma Hazelwood, Emma E Vincent

{"title":"Transcriptome-wide Mendelian randomization exploring dynamic CD4+ T cell gene expression in colorectal cancer development.","authors":"Benedita Deslandes, Xueyan Wu, Matthew A Lee, Lucy J Goudswaard, Gareth W Jones, Andrea Gsur, Annika Lindblom, Shuji Ogino, Veronika Vymetalkova, Alicja Wolk, Anna H Wu, Jeroen R Huyghe, Ulrike Peters, Amanda I Phipps, Claire E Thomas, Rish K Pai, Robert C Grant, Daniel D Buchanan, James Yarmolinsky, Marc J Gunter, Jie Zheng, Emma Hazelwood, Emma E Vincent","doi":"10.1093/jleuko/qiaf131","DOIUrl":"10.1093/jleuko/qiaf131","url":null,"abstract":"Recent research suggests higher circulating lymphocyte counts may protect against colorectal cancer (CRC). However, the role of specific lymphocyte subtypes and activation states remain unclear. CD4+ T cells - a highly dynamic lymphocyte subtype - undergo gene expression changes upon activation that are critical to their effector function. Previous studies using bulk tissue have limited our understanding of their role in CRC risk to static associations. We applied Mendelian randomization (MR) and genetic colocalisation to evaluate causal relationships of gene expression on CRC risk across multiple CD4+ T cell subtypes and activation states. Genetic proxies were obtained from single-cell transcriptomic data, allowing us to investigate the causal effect of expression of 1,805 genes across CD4+ T cell activation states on CRC risk (78,473 cases; 107,143 controls). Analyses were stratified by CRC anatomical subsites and sex, with sensitivity analyses assessing whether the observed effect estimates were likely to be CD4+ T cell-specific. We identified six genes - FADS2, FHL3, HLA-DRB1, HLA-DRB5, RPL28, and TMEM258 - with strong evidence for a causal role in CRC development (FDR-P<0.05; colocalisation H4>0.8). Causal estimates varied by CD4+ T cell subtype, activation state, CRC subsite and sex. However, many of genetic proxies used to instrument gene expression in CD4+ T cells also act as eQTLs in other tissues, highlighting the challenges of using genetic proxies to instrument tissue-specific expression changes. We demonstrate the importance of capturing the dynamic nature of CD4+ T cells in understanding CRC risk, and prioritize genes for further investigation in cancer prevention.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092110","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

Ion channels in NK cells: signaling and functions. NK细胞中的离子通道：信号传导和功能。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-09-10 DOI: 10.1093/jleuko/qiaf127

Igor Pottosin, Kathya Villatoro-Gómez, Miguel Olivas-Aguirre, Michael Schnoor, Oxana Dobrovinskaya

{"title":"Ion channels in NK cells: signaling and functions.","authors":"Igor Pottosin, Kathya Villatoro-Gómez, Miguel Olivas-Aguirre, Michael Schnoor, Oxana Dobrovinskaya","doi":"10.1093/jleuko/qiaf127","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf127","url":null,"abstract":"Ion channels are integral membrane proteins which facilitate rapid transport of small ions into and out of the cell and between organelles and cytosol. Cytolytic lymphocytes including natural killer (NK) cells principally kill virus-infected and cancer cells by releasing cytolytic granules within the immunological synapse, formed between target and effector cells. This process strongly depends on Ca2+ signaling, which in human NK cells is controlled by the phospholipase C (PLCγ)/inositol-1,4,5-triphospate receptor (IP3R)/calcium release-activated calcium channel (CRAC) axis. It is believed that CRAC, a Ca2+-selective channel within the cell membrane, is a principal mediator of Ca+ entry in non-excitable cells including immune cells. However, in addition to CRAC, the activity of other plasma membrane and organellar channels, which are permeable for Ca2+ and Na+, K+ or small anions, also plays important roles in regulating NK cell functions. In this review, we discuss the role of different ion channels in the NK-mediated immune response including members of four distinct families of K+-selective channels, transient receptor potential (TRP) channels, purinergic receptors, and pentameric ligand-gated channels that are located in the plasma membrane and lysosomes of NK cells.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033584","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

Spatial profiling reveals complex cellular responses of anti-IL5 treatment with mepolizumab in eosinophilic chronic rhinosinusitis with nasal polyposis. 空间分析揭示了mepolizumab抗il - 5治疗嗜酸性慢性鼻窦炎伴鼻息肉病的复杂细胞反应。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-09-09 DOI: 10.1093/jleuko/qiaf128

Nicholas P West, Sarah M Williams, James Sinclair, Peter Howarth, Peter K Smith, Raquel Alvarado, Peter Earls, Richard J Harvey, Amanda J Cox

{"title":"Spatial profiling reveals complex cellular responses of anti-IL5 treatment with mepolizumab in eosinophilic chronic rhinosinusitis with nasal polyposis.","authors":"Nicholas P West, Sarah M Williams, James Sinclair, Peter Howarth, Peter K Smith, Raquel Alvarado, Peter Earls, Richard J Harvey, Amanda J Cox","doi":"10.1093/jleuko/qiaf128","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf128","url":null,"abstract":"There is limited understanding of the impact of anti-IL5 treatment on nasal polyp tissue biology in chronic rhinosinusitis with nasal polyps (CRSwNP). This study examined nasal polyp tissue cellular proteome and transcriptome responses to anti-IL5 treatment in CRSwNP utilising spatial profiling. GeoMx™ Digital Spatial Profiling (DSP) of 80 proteins and 1,833 mRNA targets in the polyp stroma and the whole transcriptome (18,815 mRNA targets) in polyp epithelia was undertaken on sinonasal biopsies collected from 20 individuals with eosinophilic CRSwNP before and after 16 and 24 weeks of mepolizumab treatment. Anti-IL5 therapy in patients with eosinophilic CRSwNP had significant tissue biological impact. Treatment-related changes in polyp stroma proteins associated with checkpoint inhibition (PD-1), neutrophil degranulation (CD6b, CD44, STING1) and the innate immune system (CD14, CD68, STING, CD163) were identified in a protein interaction network. Transcriptionally, there were significant reductions in gene sets associated with the reactome-terms innate and adaptive immune system, neutrophil degranulation and TGFβ receptor signalling in epithelial to mesenchymal transition within polyp stroma, as well as enhancing antioxidant pathways. In polyp epithelia, increases in gene sets associated with the reactome-terms cilium assembly and keratinisation and a reduction in the regulation of KIT signalling were observed. Spatial profiling demonstrates that the effects of anti-IL5 treatment within nasal polyp tissue extend beyond simple eosinophil reduction to regulation of innate and adaptive immune cells and in improving epithelial barrier biology. The clinical relevance of changes to improved barrier function may relate to quality-of-life metrics observed previously with anti-IL5 treatment.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023459","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

Predominant expression of the immunosenescent biomarker CD57 on CD4+ T cells and their subsets in the older people associating with the cardiovascular disease risk factors. 免疫衰老生物标志物CD57在与心血管疾病危险因素相关的老年人CD4+ T细胞及其亚群上的主要表达

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-09-01 DOI: 10.1093/jleuko/qiaf124

Kanda Sornkayasit, Chanvit Leelayuwat, Amonrat Jumnainsong, Patcharaporn Tippayawat, Wipaporn Wongfieng, Rian Ka Praja, Sonwit Phanabamrung, Laong-Thip Raknarong, Kanin Salao, Arnone Nithichanon, Suwit Chaisri, Wisitsak Phoksawat

{"title":"Predominant expression of the immunosenescent biomarker CD57 on CD4+ T cells and their subsets in the older people associating with the cardiovascular disease risk factors.","authors":"Kanda Sornkayasit, Chanvit Leelayuwat, Amonrat Jumnainsong, Patcharaporn Tippayawat, Wipaporn Wongfieng, Rian Ka Praja, Sonwit Phanabamrung, Laong-Thip Raknarong, Kanin Salao, Arnone Nithichanon, Suwit Chaisri, Wisitsak Phoksawat","doi":"10.1093/jleuko/qiaf124","DOIUrl":"10.1093/jleuko/qiaf124","url":null,"abstract":"CD57 is one of the biomarkers for immunosenescence, and its expression increases with age. This study aimed to analyze CD4+ T cell phenotypes and cytokine production (interferon-gamma [IFN-γ] and interleukin [IL]-17) and their association with cardiovascular disease risk factors. Using multicolor flow cytometry, leftover whole blood specimens from 53 older people (≥60 yr) and 42 young individuals (≤35 yr) were analyzed. We found that older individuals had significantly higher percentages of CD4+CD57+ and CD4+ CD28- T cells than the younger group. Notably, CD57 expression was positively correlated with the number of CD4+CD28- T cells. Among the participants, older individuals with ≥1 cardiovascular disease risk factor (dyslipidemia and/or hypertension and/or diabetes mellitus) had the highest median values of CD4+CD57+, CD4+CD28-, and CD4+CD28-CD57+ T cells. Comparing the CD57+ and CD57- populations, the median percentage of IFN-γ and IL-17 from CD4+CD57+ T cells was significantly higher than those from CD4+CD57- T cells. Interestingly, older participants with ≥1 cardiovascular disease risk factor displayed a significantly higher percentage of IFN-γ-producing CD4+CD57+ T cells than older and young individuals without cardiovascular disease risk factors. In conclusion, this work reports prominent CD57 expression on CD4+ T cells and their subsets in older people. Increasing age, along with cardiovascular disease risk factors, may participate to alterations in immune function, reflected by higher levels of IFN-γ- and IL-17-producing CD4+CD57+ T cells, and may be associated with an elevated level of chronic low-grade inflammation.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957321","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

F4/80, the plasma membrane antigen of mouse macrophages, an historic journey. 小鼠巨噬细胞质膜抗原F4/80的历史征程

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-09-01 DOI: 10.1093/jleuko/qiaf126

Siamon Gordon, Annabell Roberti, Simon Yona, Hsi-Hsien Lin

引用次数: 0

The function of metalloproteinases in pathophysiology of inflammatory bowel disease and colon cancer. 金属蛋白酶在炎症性肠病和结肠癌病理生理中的作用。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-09-01 DOI: 10.1093/jleuko/qiaf116

Laura D Manzanares, Caroline J Herrnreiter, Joseph Hirst, Ronen Sumagin

{"title":"The function of metalloproteinases in pathophysiology of inflammatory bowel disease and colon cancer.","authors":"Laura D Manzanares, Caroline J Herrnreiter, Joseph Hirst, Ronen Sumagin","doi":"10.1093/jleuko/qiaf116","DOIUrl":"10.1093/jleuko/qiaf116","url":null,"abstract":"Inflammatory bowel disease (IBD) is a debilitating and symptomatic disorder of the gastrointestinal tract, featuring dysregulated inflammation, intestinal injury, and barrier dysfunction. IBD is also a risk factor for colorectal cancer (CRC), which remains a leading cause of cancer-related mortalities worldwide. Matrix metalloproteinases (MMPs) are a diverse family of proteases that play critical roles in both intestinal homeostasis and disease pathogenesis. Produced by epithelial, stromal, and immune cells, MMPs can regulate stem cell function, immune cell recruitment, microbial composition, barrier integrity, angiogenesis, and cell proliferation through extracellular matrix remodeling, cytokine activation, or direct interactions with target cells, thereby impacting the progression of both IBD and CRC. In this review we discuss the roles of MMPs in the maintenance of intestinal homeostasis and their contributions to imbalanced immune responses, epithelial integrity, and wound healing in IBD. Additionally, we highlight their contribution to epithelial-to-mesenchymal transition, angiogenesis, and metastasis in CRC. Finally, we review the potential utilization of MMPs as biomarkers for IBD/CRC diagnosis, prognosis, and treatment response. MMPs remain central to both IBD and CRC biology and present both challenges and opportunities for therapeutic intervention and disease monitoring.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835317","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

Loss of myeloperoxidase aggravates skin and joint inflammation in the mannan-induced psoriatic arthritis mouse model. 在甘露聚糖诱导的银屑病关节炎小鼠模型中，髓过氧化物酶的缺失加重了皮肤和关节炎症。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-09-01 DOI: 10.1093/jleuko/qiaf110

Mark Ringer, Antonio Maccataio, Rico Zapf, Anastasia Gaculenko, Susanne Adam, Oliver Aust, Sandra Loskarn, Julia Luther, Burak Aksoy, Vanessa Popp, Daniela Weidner, Madelaine Eck, Luis Munoz, Aline Bozec, Stefan Uderhardt, Tobias Bäuerle, Georg Schett, Gerhard Krönke, Ulrike Hüffmeier, Silke Frey, Ulrike Steffen

{"title":"Loss of myeloperoxidase aggravates skin and joint inflammation in the mannan-induced psoriatic arthritis mouse model.","authors":"Mark Ringer, Antonio Maccataio, Rico Zapf, Anastasia Gaculenko, Susanne Adam, Oliver Aust, Sandra Loskarn, Julia Luther, Burak Aksoy, Vanessa Popp, Daniela Weidner, Madelaine Eck, Luis Munoz, Aline Bozec, Stefan Uderhardt, Tobias Bäuerle, Georg Schett, Gerhard Krönke, Ulrike Hüffmeier, Silke Frey, Ulrike Steffen","doi":"10.1093/jleuko/qiaf110","DOIUrl":"10.1093/jleuko/qiaf110","url":null,"abstract":"Psoriasis is a systemic inflammatory skin disorder with a prevalence of 2% in adults. Up to 30% of affected individuals further develop psoriatic arthritis (PsA), which is characterized by additional joint inflammation. Myeloperoxidase (MPO) is strongly expressed by neutrophils and, to a lesser extent, also by other myeloid cells. MPO converts hydrogen peroxide to secondary reactive oxygen species (ROS) and is thus primarily considered to induce tissue damage. However, recent studies suggest a protective role of MPO in psoriatic diseases. We aimed to investigate the role of MPO in PsA using the mouse model of mannan-induced PsA. MPO-deficient (Mpo-/-) mice showed exacerbated skin inflammation, joint swelling, and bone degradation associated with increased infiltration of neutrophils, classically activated macrophages, and T cells as well as increased inflammatory cytokine expression in the affected tissues. In the absence or blockade of MPO, in vitro neutrophil stimulation resulted in reduced NET formation and enhanced degranulation characterized by increased neutrophil elastase (NE) activity. In addition, in vitro differentiated macrophages from Mpo-/- mice showed increased interleukin (Il)-6 mRNA expression. Altogether, our findings suggest that MPO controls inflammatory responses in PsA, at least in part, by reducing neutrophil degranulation and serine protease release and, putatively, by reducing inflammatory cytokine production by macrophages.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760324","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

S100A9 promotes inflammasome-dependent autoinflammation by blocking the degradation of SYK tyrosine kinase. S100A9通过阻断SYK酪氨酸激酶的降解促进炎性小体依赖性自身炎症。

IF 3.1 3区医学

Journal of Leukocyte Biology Pub Date : 2025-09-01 DOI: 10.1093/jleuko/qiaf129

Jonas Wolf, Yvonne Kusche, Fehime K Eroglu, Jasmin Kümmerle-Deschner, Thomas Vogl, Günter Fritz, Alexander N R Weber, Selina K Jorch, Johannes Roth, Judith Austermann

{"title":"S100A9 promotes inflammasome-dependent autoinflammation by blocking the degradation of SYK tyrosine kinase.","authors":"Jonas Wolf, Yvonne Kusche, Fehime K Eroglu, Jasmin Kümmerle-Deschner, Thomas Vogl, Günter Fritz, Alexander N R Weber, Selina K Jorch, Johannes Roth, Judith Austermann","doi":"10.1093/jleuko/qiaf129","DOIUrl":"10.1093/jleuko/qiaf129","url":null,"abstract":"Autoinflammatory diseases such as cryopyrin-associated periodic fever syndrome and familial Mediterranean fever involve an aberrant secretion of interleukin-1β due to genetic defects in the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) or pyrin inflammasomes. The regulatory mechanisms and possible interactions between inflammasome pathways remain unclear. In addition, these conditions show a high expression of the inflammatory alarmins S100A8/A9. Spleen tyrosine kinase is a known regulator of NLRP3 activity, but its connection to S100 proteins and pyrin-driven inflammation has not been described so far. This study demonstrates that S100A9 controls inflammasome activation via spleen tyrosine kinase expression in monocytes. Loss of S100A9 leads to decreased USP10 deubiquitinase expression, resulting in increased autophagosomal degradation of spleen tyrosine kinase. This impairs the S100A9-USP10-SYK pathway inhibiting NLRP3 inflammasome activation and reducing secretion of proinflammatory cytokines and S100A9. Strikingly, blocking this pathway in familial Mediterranean fever monocytes unraveled a so far unknown link between pyrin and NLRP3-driven autoinflammation. These findings identify intracellular S100A9 as a direct regulator of NLRP3 activity and a driver of autoinflammatory responses.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086126","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