Journal of Leukocyte Biology最新文献_第5页

Anti-TNF therapy in the treatment of systemic autoinflammatory diseases: the responses of innate immune cells.

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiaf026

Shuyi Wang, Rufei Xiao, Yibo Chen, Yishan Ye, Tianzhen He, Yang Yang, Xin Chen, Chon-Kit Chou

{"title":"Anti-TNF therapy in the treatment of systemic autoinflammatory diseases: the responses of innate immune cells.","authors":"Shuyi Wang, Rufei Xiao, Yibo Chen, Yishan Ye, Tianzhen He, Yang Yang, Xin Chen, Chon-Kit Chou","doi":"10.1093/jleuko/qiaf026","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf026","url":null,"abstract":"Systemic autoinflammatory diseases (SAIDs) are rare conditions resulting from innate immune system dysregulation, culminating in repetitive bouts of systemic inflammation without the presence of external or self-antigens. Most SAIDs are associated with mutations in genes affecting the innate immune response. Tumor necrosis factor (TNF) is a central player in the pathogenesis of numerous chronic inflammatory disorders, and anti-TNF therapy is widely used in the clinical management of SAIDs. TNF inhibitors block the interaction of TNF with its two receptors, TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). These inhibitors primarily target soluble TNF (sTNF), which mainly binds to TNFR1, exerting anti-inflammatory effects. Interestingly, TNF inhibitors also affect transmembrane TNF (tmTNF), which engages TNFR2 to initiate reverse signaling. This reverse signaling can activate innate immune cells, prevent apoptosis, or paradoxically inhibit the production of pro-inflammatory cytokines. TNF inhibitors also promote the release of soluble TNFR2 (sTNFR2), which neutralizes circulating TNF. Some agents targeting TNFR2 can even act as agonists, triggering reverse signaling by binding to tmTNF. While effective, prolonged use of TNF inhibitors may cause significant side effects due to the widespread expression and pleiotropic functions of TNF receptors. More thoroughly understanding of the mechanisms underlying the action of TNF inhibitors is required to develop more effective and safer treatment for SAIDs. This article reviews current studies on the role of the innate immune system in SAID pathogenesis, the impact of anti-TNF therapy on innate immune cells, and perspectives on developing improved agents targeting TNF or its receptors.","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":"143624907","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

Effect on neutrophil migration and antimicrobial functions by the Bruton's tyrosine kinase inhibitors tolebrutinib, evobrutinib, and fenebrutinib. 布鲁顿酪氨酸激酶抑制剂 tolebrutinib、evobrutinib 和 fenebrutinib 对中性粒细胞迁移和抗菌功能的影响。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae160

Mirre De Bondt, Janne Renders, Paloma Petit de Prado, Nele Berghmans, Noëmie Pörtner, Lotte Vanbrabant, Vívian Louise Soares de Oliveira, Gayel Duran, Paulien Baeten, Bieke Broux, Mieke Gouwy, Patrick Matthys, Niels Hellings, Sofie Struyf

{"title":"Effect on neutrophil migration and antimicrobial functions by the Bruton's tyrosine kinase inhibitors tolebrutinib, evobrutinib, and fenebrutinib.","authors":"Mirre De Bondt, Janne Renders, Paloma Petit de Prado, Nele Berghmans, Noëmie Pörtner, Lotte Vanbrabant, Vívian Louise Soares de Oliveira, Gayel Duran, Paulien Baeten, Bieke Broux, Mieke Gouwy, Patrick Matthys, Niels Hellings, Sofie Struyf","doi":"10.1093/jleuko/qiae160","DOIUrl":"10.1093/jleuko/qiae160","url":null,"abstract":"Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease that is still incurable. Nowadays, a variety of new drugs are being developed to prevent excessive inflammation and halt neurodegeneration. Among these are the inhibitors of Bruton's tyrosine kinase (BTK). Being indispensable for B cells, this enzyme became an appealing therapeutic target for autoimmune diseases. Recognizing the emerging importance of BTK in myeloid cells, we investigated the impact of upcoming BTK inhibitors on neutrophil functions. Although adaptive immunity in MS has been thoroughly studied, unanswered questions about the pathogenesis can be addressed by studying the effects of candidate MS drugs on innate immune cells such as neutrophils, previously overlooked in MS. In this study, we used 3 BTK inhibitors (evobrutinib, fenebrutinib, and tolebrutinib), and found that they reduce neutrophil activation by the bacterial peptide fMLF and the chemokine interleukin-8/CXCL8. Furthermore, they diminished the production of reactive oxygen species and release of neutrophil extracellular traps. Additionally, the production of CXCL8 and interleukin-1β in response to inflammatory stimuli was decreased. Inhibitory effects of the drugs on neutrophil activation were not related to toxicity. Instead, BTK inhibitors prolonged neutrophil survival in an inflammatory environment. Finally, treatment with BTK inhibitors decreased neutrophil migration toward CXCL8 in a Boyden chamber assay but not in a transendothelial setup. Also, in vivo CXCL1-induced migration was unaffected by BTK inhibitors. Collectively, this study provides novel insights into the impact of BTK inhibitors on neutrophil functions, thereby holding important implications for autoimmune or hematological diseases in which BTK is crucial.","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":"141558951","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

Distinct deregulation trends of transcriptional protein complexes in aging naive T cells. 衰老的幼稚 T 细胞中转录蛋白复合物的不同失调趋势。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae231

Emel Kökrek, Pınar Pir

{"title":"Distinct deregulation trends of transcriptional protein complexes in aging naive T cells.","authors":"Emel Kökrek, Pınar Pir","doi":"10.1093/jleuko/qiae231","DOIUrl":"10.1093/jleuko/qiae231","url":null,"abstract":"The impact of aging on T cell subsets, specifically CD4+ and CD8+ T cells, leading to immune system dysfunction has been the focus of scientific investigation due to its potential to reverse age-associated deterioration. Transcriptomic and epigenomic studies have identified the primary regulators in T cell aging. However, comprehending the underlying dynamic mechanisms requires studying these proteins with their interactors. Here, we integrated single-cell RNA sequencing data of naive CD4+ and CD8+ T cells obtained from 3 different age groups with protein-protein and domain-domain interaction networks to predict and compare the transcriptional protein complexes and identify their capacity to explain age-associated variances. Our novel approach revealed significant effects of aging on the repertoire of complexes, which remains unchanged in naive CD4+ T cells, while in naive CD8+ T cells, it diminishes. In both cell types, there was major deregulation of complexes with the same composition, involving a range of transcription factors. This aging-associated deregulation is characterized by a specific set of protein complexes in naive CD4+ T cells, but this pattern is not observed in naive CD8+ T cells. SMAD3 and BCL11A complexes emerge as key markers in defining a trajectory in aging naive CD4+ T cells. These complexes can accurately distinguish between 3 different age groups, indicating their potential as targets. The direct link between SMAD3 and FOS complexes whose regulatory role has been previously implicated in aging and MBD3 as the novel key link between SMAD3 and BCL11A complexes implicates a coordinated mechanism in age-associated deregulation.","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":"142502160","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 swarming is crucial for limiting oral mucosal infection by Candida albicans. 中性粒细胞蜂拥对限制白色念珠菌的口腔黏膜感染至关重要。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae239

Darpan Saraswat, Isolde Gina Rojas, Rohitashw Kumar, Rui Li, Ornella Salvatori, Daniel Irimia, Mira Edgerton

{"title":"Neutrophil swarming is crucial for limiting oral mucosal infection by Candida albicans.","authors":"Darpan Saraswat, Isolde Gina Rojas, Rohitashw Kumar, Rui Li, Ornella Salvatori, Daniel Irimia, Mira Edgerton","doi":"10.1093/jleuko/qiae239","DOIUrl":"10.1093/jleuko/qiae239","url":null,"abstract":"Oral mucosal colonization by Candida albicans is benign in healthy people but progresses to deeper infection, known as oropharyngeal candidiasis, that may become disseminated when combined with immunosuppression. Cortisone use and neutropenia are risk factors for invasive mucosal fungal infections; however, the mechanisms are poorly understood. Here, we identify in vivo neutrophil functional complexes known as swarms that are crucial for preventing C. albicans epithelial invasion. Anti-Ly6G antibody treatment impaired swarm formation and increased fungal infection depth, confirming the role of neutrophil swarms in limiting C. albicans invasion. Neutrophil swarm function could be disrupted by administration of resolvins, and required BLT1 (leukotriene B4 receptor 1) expression so that administration of a leukotriene synthesis inhibitor reduced neutrophil swarm size permitting C. albicans invasion beyond the basement membrane. Cortisone treatment similarly reduced neutrophil swarming behavior and BLT1 expression and delayed expression of epithelial cytokines and chemokines. Thus, swarm structures have an important function in preventing deep invasion by C. albicans within the oral mucosa and represent a mechanism for increased disease severity under immune deficient clinical settings.","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/PMC11953071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621847","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

Characterizing a Low-Density Neutrophil gene signature in acute and chronic infections and its impact on disease severity.

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-03 DOI: 10.1093/jleuko/qiaf027

Matheus Aparecido de Toledo, João Victor Souza de Lima, Reinaldo Salomão, Giuseppe G F Leite

{"title":"Characterizing a Low-Density Neutrophil gene signature in acute and chronic infections and its impact on disease severity.","authors":"Matheus Aparecido de Toledo, João Victor Souza de Lima, Reinaldo Salomão, Giuseppe G F Leite","doi":"10.1093/jleuko/qiaf027","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf027","url":null,"abstract":"Low-density neutrophils (LDNs) or polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) are involved in the pathogenesis of cancer, autoimmune and infectious diseases. They are crucial in the host-response to invading pathogens, especially during acute illness, and are associated with poor prognosis in many infectious diseases. However, their gene expression profile and contribution to disease outcomes are not well described. We conducted a meta-analysis of gene expression datasets from peripheral blood mononuclear cells (PBMCs), focusing on patients with viral and bacterial infections. We identified a consensus set of 2,798 differentially expressed genes. Among these, 49 genes were commonly found in both the neutrophil degranulation pathway and the granule lumen-specific community. To validate this signature, we evaluated its expression in RNA-seq datasets, finding consistent upregulation of 24 genes in severe infections, 17 of them overlapped with genes overexpressed in CD16int cells. We also investigated the abundance of LDN-related proteins in a PBMC proteomics dataset from a cohort of sepsis and septic shock patients. Out of the 17 genes analyzed, 13 corresponding proteins were identified, 10 of which demonstrated significantly higher abundance in sepsis and septic shock patients compared to healthy controls. In conclusion, our study identified a pattern of 17 upregulated LDN genes, common to PBMC-transcriptome and RNA-seq, and upregulated in CD16int, associated with acute infections and severe clinical outcomes, marking the first time these genes have been collectively presented as a potential signature of LDNs in relation to disease severity. Further research with prospective cohorts is needed to validate this LDN signature and explore its clinical implications.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557129","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

Suppression of NF-κB/NLRP3 by Nanoligomer Therapy Mitigates Ethanol and Advanced Age-Related Neuroinflammation.

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-02-27 DOI: 10.1093/jleuko/qiaf024

Paige E Anton, Shannon Twardy, Prashant Nagpal, Julie Moreno, Matthew A Burchill, Anushree Chatterjee, Nicolas Busquet, Michael Mesches, Elizabeth J Kovacs, Rebecca L McCullough

{"title":"Suppression of NF-κB/NLRP3 by Nanoligomer Therapy Mitigates Ethanol and Advanced Age-Related Neuroinflammation.","authors":"Paige E Anton, Shannon Twardy, Prashant Nagpal, Julie Moreno, Matthew A Burchill, Anushree Chatterjee, Nicolas Busquet, Michael Mesches, Elizabeth J Kovacs, Rebecca L McCullough","doi":"10.1093/jleuko/qiaf024","DOIUrl":"10.1093/jleuko/qiaf024","url":null,"abstract":"Binge alcohol use is increasing among aged adults (>65 years). Alcohol-related toxicity in aged adults is associated with neurodegeneration, yet the molecular underpinnings of this age-related sensitivity to alcohol are not well described. Studies utilizing rodent models of neurodegenerative disease reveal heightened activation of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Nod like receptor 3 (NLRP3) mediate microglia activation and associated neuronal injury. Our group, and others, have implicated hippocampal-resident microglia as key producers of inflammatory mediators, yet the link between inflammation and neurodegeneration has not been established in models of binge ethanol exposure and advanced age. Here, we report binge ethanol increased the proportion of NLRP3+ microglia in the hippocampus of aged (18-20 months) female C57BL/6N mice compared to young (3-4 months). In primary microglia, ethanol-induced expression of reactivity markers and NLRP3 inflammasome activation were more pronounced in microglia from aged mice compared to young. Using a NLRP3-specific inhibitor (OLT1177) and a novel brain-penetrant Nanoligomer that inhibits NF-κB and NLRP3 translation (SB_NI_112), we find ethanol-induced microglial reactivity can be attenuated by OLT1177 and SB_NI_112 in microglia from aged mice. In a model of intermittent binge ethanol exposure, SB_NI_112 prevented ethanol-mediated microglia reactivity, IL-1β production, and tau hyperphosphorylation in the hippocampus of aged mice. These data suggest early indicators of neurodegeneration occurring with advanced age and binge ethanol exposure are driven by NF-κB and NLRP3. Further investigation is warranted to explore the use of targeted immunosuppression via Nanoligomers to attenuate neuroinflammation after alcohol consumption in the aging populations.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557152","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

High-dimensional spectral flow cytometry of activation and phagocytosis by peripheral human polymorphonuclear leukocytes.

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-02-26 DOI: 10.1093/jleuko/qiaf025

Evan R Lamb, Ian J Glomski, Taylor A Harper, Michael D Solga, Alison K Criss

{"title":"High-dimensional spectral flow cytometry of activation and phagocytosis by peripheral human polymorphonuclear leukocytes.","authors":"Evan R Lamb, Ian J Glomski, Taylor A Harper, Michael D Solga, Alison K Criss","doi":"10.1093/jleuko/qiaf025","DOIUrl":"10.1093/jleuko/qiaf025","url":null,"abstract":"Polymorphonuclear leukocytes (PMNs) are terminally differentiated phagocytes with pivotal roles in infection, inflammation, tissue injury, and resolution. PMNs display a breadth of responses to diverse endogenous and exogenous stimuli, making understanding of these innate immune responders vital yet challenging to achieve. Here, we report a 22-color spectral flow cytometry panel to profile primary human PMNs for surface marker expression of activation, degranulation, phagocytosis, migration, chemotaxis, and interaction with fluorescently labeled cargo. We demonstrate the surface marker response of PMNs to phorbol ester stimulation compared to untreated controls in an adherent PMN model with additional analysis of intra- and inter-subject variability. PMNs challenged with the Gram-negative bacterial pathogen Neisseria gonorrhoeae revealed infectious dose-dependent changes in surface marker expression in bulk, population-level analysis. Imaging flow cytometry complemented spectral cytometry, demonstrating that fluorescence signal from labeled bacteria corresponded with bacterial burden on a per-cell basis. Spectral flow cytometry subsequently identified surface markers which varied with direct PMN-bacterium association as well as those which varied in the presence of bacteria but without phagocytosis. This spectral panel protocol highlights best practices for efficient customization and is compatible with downstream approaches such as spectral cell sorting and single-cell RNA-sequencing for applicability to diverse research questions in the field of PMN biology.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557146","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

Enhanced Siglec-8 and HLA-DR and Reduced CRTH2 Surface Expression, Highlight a Distinct Phenotypic Signature of Circulating Eosinophils in Atopic Dermatitis.

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-02-25 DOI: 10.1093/jleuko/qiaf023

Frédéric Dezoteux, Pierre Marcant, Arnaud Dendooven, Émeline Delaunay, Stéphane Esnault, Jacques Trauet, Guillaume Lefevre, Delphine Staumont-Salle

{"title":"Enhanced Siglec-8 and HLA-DR and Reduced CRTH2 Surface Expression, Highlight a Distinct Phenotypic Signature of Circulating Eosinophils in Atopic Dermatitis.","authors":"Frédéric Dezoteux, Pierre Marcant, Arnaud Dendooven, Émeline Delaunay, Stéphane Esnault, Jacques Trauet, Guillaume Lefevre, Delphine Staumont-Salle","doi":"10.1093/jleuko/qiaf023","DOIUrl":"10.1093/jleuko/qiaf023","url":null,"abstract":"Atopic dermatitis (AD) as well as other type 2 immune response (T2) diseases are often linked to elevated eosinophil (Eos) levels in the blood. Although the role of Eos in AD pathophysiology is suspected, it remains unclear. The development of new treatments targeting the T2 response, particularly cytokines involved in Eos activation and chemotaxis, makes it necessary to identify potential Eos profiles in AD that may respond to these treatments. A prospective study was conducted comparing blood Eos phenotypes in moderate-to-severe AD patients (n=19) without recent systemic treatment to healthy individuals (HI, n=19). The primary outcome was the membranous phenotypic signature of Eos, assessed by flow cytometry. Most AD patients (84%) had early onset in childhood, a severe disease (mean SCORAD of 57.5), and elevated blood Eos counts (310 per µl in AD vs 120 in HI, p<0.0001). AD patients exhibited lower CRTH2 on Eos but higher levels of HLA-DR and Siglec-8 compared to HI. Other surface proteins showed no significant differences. Clustering analysis confirmed increased Siglec-8 in AD patients. Additionally, AD patients had higher serum levels of T2 immune response-markers as eotaxin-2, IL-5, IL-3, and TARC. Circulating Eos in AD patients show a distinct phenotypic profile, suggesting a role in AD pathophysiology and potential involvement in differential treatment responses.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492296","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

MiR-340-5p alleviates AECOPD by targeting MAP3K2 via Qingjin Huatan Decoction therapy.

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-02-20 DOI: 10.1093/jleuko/qiaf021

Mei Zhao, Zhijian Huang, Jinghui Zheng, Wanying Li, Yunqing Zhong, Tun Ouyang

{"title":"MiR-340-5p alleviates AECOPD by targeting MAP3K2 via Qingjin Huatan Decoction therapy.","authors":"Mei Zhao, Zhijian Huang, Jinghui Zheng, Wanying Li, Yunqing Zhong, Tun Ouyang","doi":"10.1093/jleuko/qiaf021","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf021","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) features persistent inflammation and restricted airflow, with acute exacerbations of COPD (AECOPD) significantly worsening patient outcomes. This study aims to explore the role of Qingjin Huatan Decoction (QJHTT) on AECOPD with the syndrome of phlegm-heat obstruction of the lung.AECOPD was induced in male Sprague-Dawley rats using lipopolysaccharide (LPS) and cigarette smoke exposure. Rats were treated with varying doses of QJHTT. miR-340-5p expression was quantified using qPCR. Lung histopathology was assessed with hematoxylin and eosin (HE) staining, and interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA).. The effects on cell viability and apoptosis in primary airway epithelial cells were evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The dual-luciferase reporter assay validated the interaction between miR-340-5p and mitogen-activated protein kinase kinase kinase 2 (MAP3K2), and protein expression was analyzed by Western blot.QJHTT improved lung histopathology, reducing inflammatory cell infiltration and alveolar damage. ELISA results showed reduced inflammatory cytokines levels in QJHTT-treated groups (P < 0.05). qPCR analysis demonstrated that QJHTT upregulated miR-340-5p expression (P < 0.05). miR-340-5p mimic enhanced cell viability and reduced apoptosis in primary airway epithelial cells (P < 0.05). Dual-luciferase reporter assay confirmed that miR-340-5p directly targets MAP3K2, leading to its downregulation (P < 0.05). QJHTT exerts therapeutic effects in phlegm-heat obstructing the lung type of AECOPD through upregulating miR-340-5p and inhibiting MAP3K2. This study highlights the QJHTT and miR-340-5p/MAP3K2 pathway for this disease treatment.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458292","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

Histones HIST1 genes and tumor infiltrating lymphocytes in a child with gamma delta T cell acute lymphoblastic leukemia by single-cell sequencing.

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-02-20 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":"Histones HIST1 genes and tumor infiltrating lymphocytes in a child with gamma delta 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":"https://doi.org/10.1093/jleuko/qiaf022","url":null,"abstract":"Gamma delta 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 histones HIST1 genes and gamma delta 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 gamma delta tumor infiltrating lymphocytes in γδ T-ALL cells for developing novel therapeutic approaches.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-20","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