Journal of Leukocyte Biology最新文献_第6页

DLL4+ neutrophils induce alveolar macrophages to cause ADAM-17-mediated endothelial barrier disruption and the increase of ICAM1hiCXCR1lo neutrophils in sepsis. 脓毒症中DLL4+中性粒细胞诱导肺泡巨噬细胞引起adam -17介导的内皮屏障破坏和ICAM1hiCXCR1lo中性粒细胞的增加

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag097

Hui Jin, Saoirse Holland, Alok Jha, Monowar Aziz, Ping Wang

{"title":"DLL4+ neutrophils induce alveolar macrophages to cause ADAM-17-mediated endothelial barrier disruption and the increase of ICAM1hiCXCR1lo neutrophils in sepsis.","authors":"Hui Jin, Saoirse Holland, Alok Jha, Monowar Aziz, Ping Wang","doi":"10.1093/jleuko/qiag097","DOIUrl":"10.1093/jleuko/qiag097","url":null,"abstract":"Sepsis remains a leading cause of death. Reverse migrated neutrophils, characterized as ICAM1hiCXCR1lo, have been recognized as a key driver of systemic inflammation and organ injury in sepsis. We discovered a distinct delta-like ligand 4-positive (DLL4+) subset of neutrophils that accumulate in the lungs, contributing to lung injury; however, the underlying mechanism is less understood. In sepsis, ICAM1hiCXCR1lo neutrophils, being hyperactive, are detrimental. Here, we investigated how DLL4+ neutrophils activate alveolar macrophages (AMs) to cause endothelial cell barrier disruption and promote neutrophil reverse migration. AMs were treated with DLL4+ neutrophils or recombinant mouse DLL4, and a disintegrin and metalloprotease (ADAM17) generated by AMs was assessed at both mRNA and protein levels. Conditioned medium was subsequently applied to pulmonary vascular endothelial cells (pVECs); junctional adhesion molecule-C (JAM-C) protein was detected by Western blot assays; and ICAM1hiCXCR1lo neutrophils were detected by flow cytometry. We demonstrate that during sepsis induced by cecal ligation and puncture (CLP), DLL4+ neutrophils interact with AMs via the Notch1 pathway, leading to increase of ADAM17 expression. ADAM17 decreased JAM-C on pVECs, causing endothelial barrier disruption and ICAM1hiCXCR1lo neutrophil generation. A small-molecule inhibitor of ADAM17 effectively preserved pulmonary endothelial barrier integrity and reduced ICAM1hiCXCR1lo neutrophil accumulation. Importantly, we have developed a novel DLL4-Notch1 inhibitory peptide (NDI) that effectively suppresses ADAM17 expression, restores JAM-C, and reduces ICAM1hiCXCR1lo neutrophil accumulation in sepsis. These findings identify DLL4+ neutrophils as critical inflammatory mediators that exacerbate systemic inflammation and worsen sepsis, and highlight the DLL4-Notch1-ADAM17 axis as a promising therapeutic target.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421666","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

Correction to: IL-27 signaling negatively regulates FcɛRI-mediated mast cell activation and allergic response. 修正：IL-27信号负调控Fc - i介导的肥大细胞活化和过敏反应。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag089

引用次数: 0

Recombinant human interleukin-32γ facilitates macrophage phagocytosis of Streptococcus pneumoniae by activating nuclear factor kappa B-soluble epoxide hydrolase pathway. rhIL-32γ通过激活NF-κ b可溶性环氧化物水解酶途径促进肺炎链球菌巨噬细胞吞噬。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag093

Longying Liang, Tingting Li, Weiwei Zhang, Chengmin Deng, Longze Zhang, Kaifeng Wu, Shifei Yao

{"title":"Recombinant human interleukin-32γ facilitates macrophage phagocytosis of Streptococcus pneumoniae by activating nuclear factor kappa B-soluble epoxide hydrolase pathway.","authors":"Longying Liang, Tingting Li, Weiwei Zhang, Chengmin Deng, Longze Zhang, Kaifeng Wu, Shifei Yao","doi":"10.1093/jleuko/qiag093","DOIUrl":"10.1093/jleuko/qiag093","url":null,"abstract":"Interleukin-32 is recognized as a potent proinflammatory mediator in various infectious contexts; however, its precise contribution to host defense against Streptococcus pneumoniae (S.pn) remains to be fully elucidated. This study demonstrates that S.pn challenge robustly upregulates interleukin-32 expression in human peripheral blood mononuclear cells and THP-1 cells. Functional assays reveal that exogenous recombinant human interleukin-32γ significantly potentiates the phagocytic activity of both murine (RAW 264.7) and human (THP-1-derived) macrophages against S.pn. Mechanistically, recombinant human interleukin-32γ-induced phagocytosis is mediated by the upregulation and secretion of soluble epoxide hydrolase (sEH), a process contingent upon the activation of the nuclear factor κB (NF-κB) signaling pathway. Furthermore, pharmacological inhibition of either NF-κB or sEH effectively abrogates the prophagocytic effects of recombinant human interleukin-32γ, confirming the functional requirement of the NF-κB-sEH axis in this response. Collectively, these results elucidate a novel interleukin-32γ-NF-κB-sEH regulatory cascade that facilitates macrophage-mediated bacterial clearance, thereby identifying a potential therapeutic target for the management of pneumococcal infections.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421683","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

Correction to: ICAM-1 and vascular matrices coordinate skin S1 macrophage formation from blood PDGFRα lineage monocyte. 修正：ICAM-1和血管基质协调血液PDGFRα系单核细胞形成皮肤S1巨噬细胞。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag101

引用次数: 0

Rhinovirus infection may contribute to esophageal inflammation in eosinophilic esophagitis. 鼻病毒感染可能导致嗜酸性食管炎的食管炎症。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag095

Paul S Fichtinger, Samuel G Sonsalla, Mats W Johansson, Amali E Samarasinghe, Luis D Lomeli, Sameer K Mathur

{"title":"Rhinovirus infection may contribute to esophageal inflammation in eosinophilic esophagitis.","authors":"Paul S Fichtinger, Samuel G Sonsalla, Mats W Johansson, Amali E Samarasinghe, Luis D Lomeli, Sameer K Mathur","doi":"10.1093/jleuko/qiag095","DOIUrl":"10.1093/jleuko/qiag095","url":null,"abstract":"Eosinophil esophagitis (EoE) shares many epidemiologic and pathophysiologic characteristics with other allergic diseases, especially allergic asthma. Because rhinovirus (RV) infection is known to contribute to inflammation in allergic asthma, we sought to investigate whether RV might also contribute to esophageal inflammation in EoE through epithelial activation. In vitro cultures of primary esophageal epithelial cells and a human nontransformed immortalized esophageal epithelial cell line (EPC2-hTERT) grown submerged or at air-liquid interface were infected with RV-A1a or RV-A16. In addition, we added interleukin (IL)-13 to mimic EoE conditions. RV-binding receptors, RV replication, and interferon lambda-1 (IFNL1) response to infection were measured. RNA sequencing (RNA-seq) on RV-infected EPC2-hTERT cultures was performed for Gene Ontology analysis and compared with published RNA-seq data of esophageal biopsies from EoE patients. Both RV receptors were expressed by esophageal cells. After infection, we observed higher RV viral gene expression, indicative of active replication. IL-13 had little effect on replication in monolayers but was required in air-liquid interface for replication to occur. Interferon lambda-1 (IFNL1) messenger RNA was induced by RV-A1a in both cell types and IFNL1 protein was increased in IL-13-treated EPC2-hTERT monolayers. Gene Ontology analysis of our in vitro experimental model highlighted virus-induced processes and increased IFN activity. In addition, we found overlapping genes between our RNA-seq results of EPC2-hTERT cells and publicly available RNA-seq data from esophageal biopsies of patients with EoE versus healthy control donors. Our data suggest the possibility that viruses such as RV may contribute to esophageal inflammation and play an important role in the inception and/or persistence of EoE.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421633","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

SHIP blocks (MDP + LPS)-induced synergy in macrophages independent of catalytic activity. SHIP阻断（MDP+LPS）诱导的巨噬细胞协同作用，不依赖于催化活性。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag090

Yvonne C F Pang, Susan C Menzies, Laura M Sly

{"title":"SHIP blocks (MDP + LPS)-induced synergy in macrophages independent of catalytic activity.","authors":"Yvonne C F Pang, Susan C Menzies, Laura M Sly","doi":"10.1093/jleuko/qiag090","DOIUrl":"10.1093/jleuko/qiag090","url":null,"abstract":"Macrophages coordinate cytokine responses by integrating signals from pattern recognition receptors including NOD2 and TLR4. NOD2 detects muramyl dipeptide derived from bacterial peptidoglycan, and TLR4 recognizes lipopolysaccharide in the outer membrane of Gram-negative bacteria. NOD2 and TLR4 signals synergize to enhance cytokine production in myeloid cells. While synergy can support host defense, it must be regulated to minimize the risk of excessive inflammation. The lipid phosphatase SHIP, a negative regulator of Class I PI3Ks, reduces inflammatory signaling, but its role during NOD2-TLR4 co-stimulation remains undefined. We found that SHIP limits IL-1β production by blocking synergy in bone marrow-derived macrophages co-stimulated with muramyl dipeptide and lipopolysaccharide. SHIP-/- macrophages showed a synergistic increase in IL-1β that was not evident in SHIP+/+ macrophages. Moreover, reducing SHIP protein concentrations by differentiation in different growth factors, IL-4 treatment, or siRNAs enabled synergy for IL-1β production in SHIP+/+ macrophages. Pharmacologic inhibition of SHIP's catalytic activity did not promote synergy, and similarly, blocking PI3K had no effect, suggesting that the response is independent of SHIP's phosphatase activity. Synergy for IL-1β production was dependent on NOD2 signaling despite NOD2 stimulation alone resulting in little to no IL-1β. Moreover, IL-1β was selectively enhanced in SHIP-/- macrophages during co-stimulation with MDP and LPS, or when MDP stimulation preceded LPS. These findings identify SHIP's adaptor function as a negative regulator of IL-1β induced by NOD2-TLR4 co-stimulation in macrophages, and suggest that SHIP acts as a gatekeeper for macrophage IL-1β during early innate immune activation.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337762","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

Editor's Note on 'Sialoglycoproteins adsorbed by Pseudomonas aeruginosa facilitate their survival by impeding neutrophil extracellular trap through siglec-9'. 编者注：铜绿假单胞菌吸附的唾液糖蛋白通过siglece -9阻碍中性粒细胞胞外陷阱，从而促进其存活。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag070

引用次数: 0

Lysosome-induced increase in intracellular granularity of leukocytes: a key morphological biomarker for early sepsis in cell population data. 溶酶体诱导的细胞内白细胞粒度增加：细胞群数据中早期脓毒症的关键形态学生物标志物。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag098

Huan Qi, Xiaomei Zhang, Yushuai Ma, Shiyao Pan, Chuanjian Wu, Bo Ye, Yi Ye, Xueying Yang, Shihong Zhang, Keqian Xu

{"title":"Lysosome-induced increase in intracellular granularity of leukocytes: a key morphological biomarker for early sepsis in cell population data.","authors":"Huan Qi, Xiaomei Zhang, Yushuai Ma, Shiyao Pan, Chuanjian Wu, Bo Ye, Yi Ye, Xueying Yang, Shihong Zhang, Keqian Xu","doi":"10.1093/jleuko/qiag098","DOIUrl":"10.1093/jleuko/qiag098","url":null,"abstract":"Early and rapid identification of sepsis is critical for improving clinical outcomes; however, reliable real-time biomarkers remain unavailable. The scattergram parameters of peripheral blood circulating leukocytes are altered during infection and sepsis. This study aims to explore the cellular biological characteristics underlying these changes, with a particular focus on morphological complexity. An in vitro human whole-blood infection model was constructed by stimulating isolated healthy human peripheral blood with lipopolysaccharide (LPS). Concurrently, a sepsis mouse model was established via intraperitoneal LPS injection. Subsequently, protein kinase C and myeloid differentiation primary-response protein 88 (MyD88) inhibitors were administered separately to establish corresponding inhibition models in mice. The total lysosomal contents in leukocytes and monocytes were then detected to analyze the intrinsic mechanism responsible for the sepsis-associated changes in the scattergram parameters. The results indicated elevated lysosome counts in leukocytes raised N_WBC_SFL_W, whereas those in monocytes drove higher D_Mon_SSC_W under septic conditions. This study reveals that the increased lysosomal content is the primary cause of the heightened number of cytoplasmic granules in leukocytes during sepsis. Furthermore, it clarifies that the characteristic changes in the scattergram parameters N_WBC_SFL_W and D_Mon_SSC_W detected through hematological analysis are a consequence of alterations in the lysosomal content. Collectively, our finding demonstrates that sepsis-induced alterations in leukocytes are hematological manifestations of aberrant lysosomal expansion, providing novel mechanistic insights for sepsis diagnosis and potential therapeutic monitoring.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471179","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

HIF-1α in macrophage polarization: roles in immunometabolism and autoimmune diseases. 巨噬细胞极化中的HIF-1α：在免疫代谢和自身免疫性疾病中的作用

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag082

Dongye Li, Xihao Pan, ZiJin He, Jingru Cui, Runhe Zhu, Dadong Guo

{"title":"HIF-1α in macrophage polarization: roles in immunometabolism and autoimmune diseases.","authors":"Dongye Li, Xihao Pan, ZiJin He, Jingru Cui, Runhe Zhu, Dadong Guo","doi":"10.1093/jleuko/qiag082","DOIUrl":"10.1093/jleuko/qiag082","url":null,"abstract":"Hypoxia-inducible factor-1α (HIF-1α) is a central regulator of cellular responses to hypoxia and plays a pivotal role in immune cell activation and functional reprogramming. This review summarizes how HIF-1α modulates inflammatory responses through metabolic regulation and examines its mechanistic involvement in autoimmune diseases. Under normoxic conditions, HIF-1α is rapidly degraded, whereas hypoxia, inflammation, or metabolic stress stabilizes the protein, allowing its nuclear translocation and activation of glycolysis-related genes. This shift drives immune cells from oxidative metabolism to glycolysis, supporting rapid energy production and promoting inflammation-associated functional states. Consequently, HIF-1α enhances the production of inflammatory mediators and forms positive feedback loops with inflammatory signaling pathways, influencing immune cell migration, survival, and function. Aberrant activation of HIF-1α is closely associated with disease activity in autoimmune disorders, such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis, contributing to immune imbalance and tissue damage. However, its effects are context-dependent; in conditions like inflammatory bowel disease and uveitis, moderate activation may exert protective roles. Therefore, therapeutic strategies require precise, context-specific modulation rather than simple inhibition or activation. Although current drug development targeting HIF-1α focuses mainly on oncology, emerging approaches-including small molecule inhibitors, nanodelivery systems, and gene therapy-highlight its potential in autoimmune disease treatment. Overall, HIF-1α serves as a key link between hypoxia, metabolism, and immune regulation.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271844","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

CD43: recent advances and emerging functions. CD43：最新进展和新功能。

IF 3.4 3区医学

Journal of Leukocyte Biology Pub Date : 2026-07-03 DOI: 10.1093/jleuko/qiag084

Mariana Diupotex, Veronica Rojo-Leon, Luis Eduardo Chipres-Naranjo, Estefanía Alemán-Navarro, Emiliano Rubio-Blancas, Alejandra Carrillo-Carlos, Gabriel Ramírez-Vilchis, Jazmin López-Acosta, José Luis Maravillas-Montero, Yvonne Rosenstein

{"title":"CD43: recent advances and emerging functions.","authors":"Mariana Diupotex, Veronica Rojo-Leon, Luis Eduardo Chipres-Naranjo, Estefanía Alemán-Navarro, Emiliano Rubio-Blancas, Alejandra Carrillo-Carlos, Gabriel Ramírez-Vilchis, Jazmin López-Acosta, José Luis Maravillas-Montero, Yvonne Rosenstein","doi":"10.1093/jleuko/qiag084","DOIUrl":"10.1093/jleuko/qiag084","url":null,"abstract":"Originally characterized for its roles in T-cell activation and adhesion, CD43 is a prominent mucin-like sialoglycoprotein expressed on hematopoietic cells. CD43 is broadly expressed across leukocyte populations, with its levels, molecular configuration, and ligand interactions varying by cell type, activation state, and differentiation. Growing evidence indicates that CD43 functions as a context-dependent regulator, integrating microenvironmental cues and dynamic glycosylation states with the biophysical organization of the cell surface and intracellular signaling. CD43 simultaneously participates in immune activation, regulation, and dysfunction, depending on the cellular and environmental context. CD43 is associated with distinct, sometimes contrasting, functional outcomes across diverse physiological and pathological settings. For instance, it has been linked to altered leukocyte trafficking and activation, while in infectious diseases, it influences host-pathogen interactions and the balance between protective immunity and immunopathology. Furthermore, in cancer, changes in CD43 signaling, glycosylation, and ligand engagement modulate immune recognition, effector responses, and inflammatory processes, contributing to immune evasion. Here, we review current knowledge on the regulation of CD43 expression, its structural organization, and ligand interactions. We discuss the potential role of CD43 across different disease settings, proposing it as a dynamic, adaptable regulator of immune responses and a potential therapeutic target in immune-mediated diseases.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338930","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