Daniel I Petkov, Summer Siddiqui, David X Liu, Carolina Allers, Peter J Didier, Woong-Ki Kim, Elizabeth S Didier, Marcelo J Kuroda
{"title":"SIV infection induces aging-like alterations in cardiac cellularity and macrophage populations of rhesus macaques.","authors":"Daniel I Petkov, Summer Siddiqui, David X Liu, Carolina Allers, Peter J Didier, Woong-Ki Kim, Elizabeth S Didier, Marcelo J Kuroda","doi":"10.1093/jleuko/qiag069","DOIUrl":"10.1093/jleuko/qiag069","url":null,"abstract":"<p><p>People living with HIV experience an earlier risk for onset of aging-related chronic inflammatory comorbidities, including cardiovascular disease. We previously showed that the proportion of macrophages was higher in the heart of older rhesus macaques (Macaca mulatta) with normal histopathology as well as in all age groups of macaques with cardiac pathology. In the present study, we investigated the effects of simian immunodeficiency virus (SIV) infection on cell density and macrophages in heart tissues of adult rhesus macaques. Heart tissues were evaluated by hematoxylin and eosin staining and immunofluorescence staining to assess the number and phenotype of heart macrophages that could change with SIV infection. Cardiac cellularity was lower in hearts of SIV-infected young and adult macaques, as well as in uninfected aged macaques, compared with uninfected adult rhesus macaques. This lower cellularity was associated with higher percentages of CD163+ macrophages in hearts of SIV-infected young adult macaques, similar to that of uninfected aged macaques. Higher percentages of CD163+ macrophages were also observed in diseased hearts of both SIV-infected and uninfected adult animals that appeared to be short-lived macrophages, based on 5-bromo-2'-deoxyuridine labeling. In contrast, macrophages retaining in vivo-administered dextran, indicative of long-lived macrophages, predominated among cardiac macrophages in both SIV-infected and uninfected animals of all ages. Together, these results suggest SIV infection induces changes in cardiac cellularity and macrophage composition that resemble those observed during aging. This rhesus macaque model supports continued studies to further dissect the shifting dynamics of macrophage subsets and their role in heart adaptations in response to HIV infection and aging.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13316664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163537","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}
{"title":"Beyond suppression: the plasticity, dysfunction, and therapeutic reprogramming of regulatory T cells in inflammatory bowel disease.","authors":"Yunting Shao, Shaochen Yu, Mengjie Zhang, Yuting Huang, Ziyue Dou, Beibei Tian, Jian Lu","doi":"10.1093/jleuko/qiag067","DOIUrl":"10.1093/jleuko/qiag067","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gut, whose pathogenesis is closely related to immune dysregulation. Regulatory T cells (Tregs), as a key cell population maintaining intestinal immune tolerance, exhibit not only reduced frequency but, more critically, profound functional deficiencies, including the generation of proinflammatory ex-Tregs, and loss of lineage stability in the inflamed gut microenvironment of IBD. This review systematically delineates the sophisticated biological characteristics of Tregs, with a particular focus on the epigenetic and metabolic checkpoints that govern their stability. We critically summarize the aberrant changes of Tregs in IBD, emphasizing mechanisms such as inflammatory cytokine-induced Treg plasticity (eg Th1-like or Th17-like conversion) and microbiota-metabolite axis-mediated functional modulation. Furthermore, we provide an in-depth analysis of emerging therapeutic strategies aimed at restoring Treg suppressive capacity, including selective cytokine therapy (eg low-dose/engineered IL-2), adoptive transfer of engineered antigen-specific Tregs (including CAR-Tregs), microbiome/dietary interventions, and pharmacological modulation of Treg differentiation. We also discuss the disrupted crosstalk between Tregs and other innate and adaptive immune cells within the IBD milieu. Finally, this review highlights how cutting-edge technologies like single-cell multiomics and spatial transcriptomics are delineating the heterogeneous landscape and uncovering novel, disease-specific Treg subpopulations, thereby paving the way for precise Treg-targeting therapies. Unlike previous reviews that broadly catalog Treg abnormalities, this review offers a refined conceptual framework centered on the critical distinction between lineage-defective ex-Tregs and exhausted effector Tregs, and integrates recent multiomics insights to redefine Treg functional failure in IBD.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042616","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}
Javier Orozco-Cordoba, Julio Y Anaya-Covarrubias, Minerva D Santiago, Diego Zamora, Sonia Roman, Arturo Panduro, Julio César Carrero, Nora A Fierro
{"title":"Conjugated bilirubin reduces hepatitis E virus infectivity by modulating immunometabolic processes.","authors":"Javier Orozco-Cordoba, Julio Y Anaya-Covarrubias, Minerva D Santiago, Diego Zamora, Sonia Roman, Arturo Panduro, Julio César Carrero, Nora A Fierro","doi":"10.1093/jleuko/qiag078","DOIUrl":"10.1093/jleuko/qiag078","url":null,"abstract":"<p><p>Despite the landmark discovery of the hepatitis E virus (HEV) four decades ago and its status as the leading cause of viral hepatitis worldwide, the infection remains overlooked in numerous countries. Currently, there are no approved treatments for hepatitis E or licensed vaccines available for global distribution. The clinical presentation of infection is influenced by the host's immune response and may also be affected by metabolic factors. We previously reported an immunomodulatory role for conjugated bilirubin (cBR) in hepatitis A virus infection, and antiviral effects of this metabolite have been proposed. However, the impact of cBR on HEV infectivity and the mechanisms underlying this effect have yet to be elucidated. By combining (i) ex vivo analysis of HEV-infected patients, (ii) in vitro antigenic restimulation of peripheral blood mononuclear cells (PBMCs) cultured with different cBR doses, and (iii) in vitro infection of permissive cell lines, we found that cBR concentrations of 2 mg/dL lowered viral titers and increased IFN-γ release in patients with acute infection. Furthermore, antigenic restimulation of PBMCs cultured with 2 mg/dL cBR promoted positive interactions between TNF-α and metabolic signaling proteins such as Akt and ERK. Moreover, cBR induced the overproduction of IFN-γ by CD8+ T cells from individuals with prior HEV exposure and decreased viral titers in both acute and chronic infection models at concentrations greater than or equal to 0.3 mg/dL. These findings demonstrate that during HEV infection, cBR plays a significant role in modulating the interaction between immune and metabolic components, ultimately influencing viral infectivity.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217760","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}
Raúl F Reyes-Huerta, Rosa G Rebollar-Vega, Jiram Torres-Ruiz, Diana Gómez-Martín, José L Maravillas-Montero
{"title":"The role of B cells in idiopathic inflammatory myopathies.","authors":"Raúl F Reyes-Huerta, Rosa G Rebollar-Vega, Jiram Torres-Ruiz, Diana Gómez-Martín, José L Maravillas-Montero","doi":"10.1093/jleuko/qiag071","DOIUrl":"10.1093/jleuko/qiag071","url":null,"abstract":"<p><p>Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders characterized by skeletal muscle inflammation and systemic immune activation. Although traditionally viewed as T cell-driven diseases, recent evidence suggests that B lymphocytes may also contribute to disease mechanisms through both antibody-dependent and noncanonical pathways. Beyond their role in autoantibody production, B cells might influence immune regulation by modulating cytokine networks, presenting antigens, and interacting with T cells and stromal elements within inflamed tissues. These findings have prompted renewed interest in understanding B cell heterogeneity and its possible impact on the initiation and maintenance of chronic inflammation in idiopathic inflammatory myopathies. However, the exact contribution of these cells to tissue damage and clinical variability remains uncertain. Advances in high-dimensional cytometry, transcriptomics, and tissue profiling are beginning to delineate distinct B cell signatures associated with disease activity, yet the causal links to pathogenesis remain unclear. The observed clinical benefit of B cell-depleting therapies, though variable among patients, reinforces their potential relevance while underscoring the complexity of immune interactions in idiopathic inflammatory myopathies. This review aims to synthesize current knowledge on B cells in idiopathic inflammatory myopathies and to discuss how emerging mechanistic insights could refine our understanding of disease heterogeneity and guide future therapeutic approaches.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138401","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}
Blanca E Callejas, Jared Schlechte, James A Sousa, Natalie Andonian, Lucas Kraemer, Kyle Flannigan, Eve Higgins, Arthur Wang, Ryan Rosentreter, Braedon McDonald, Remo Panaccione, Derek M McKay
{"title":"High-dimensional single-cell mass cytometry analysis of IL-4 treated human macrophages reveals heterogeneity and a CD206high anticolitic subset.","authors":"Blanca E Callejas, Jared Schlechte, James A Sousa, Natalie Andonian, Lucas Kraemer, Kyle Flannigan, Eve Higgins, Arthur Wang, Ryan Rosentreter, Braedon McDonald, Remo Panaccione, Derek M McKay","doi":"10.1093/jleuko/qiag075","DOIUrl":"https://doi.org/10.1093/jleuko/qiag075","url":null,"abstract":"<p><p>Autologous cell therapy is a patient-embraced approach to inflammatory disease. Murine models demonstrate that alternatively activated (or regulatory) macrophages can reduce the severity of disease, and human macrophages (M0) educated with interleukin-4 (M(IL4)) limit murine colitis. M0 and M(IL4) from healthy donors and individuals with Crohn's disease (active or remission) were assessed by qPCR, characterized by a time-of-flight mass cytometry (CyTOF) comparison of 16 myeloid marker molecules expression, and subtypes of M(IL4)s tested in the murine dinitrobenzene sulfonic acid (DNBS) model of colitis and in vitro co-culture with T cells. Most macrophage preparations responded to IL-4 by increasing CD206, CCL18 and RAMP1 mRNA expression and produced mediators that promoted epithelial repair in a wound assay with the human CaCo2 epithelial line. Single-cell clustering by FlowSOM defined 8 distinct subpopulations (meta-clusters) of macrophages, the proportions of which were unaffected by biological sex, age or cryopreservation: meta-cluster 4 (CD206highPD-L1highHLA-DRhigh) represented 20 to 40% of M0s, with a higher proportion in controls compared with active Crohn's disease. IL-4 treatment significantly expanded meta-cluster 4 in all M0s. Transfer of M(IL4)-CD206high (ie, predominantly meta-cluster 4) into rag1-/- mice significantly reduced DNBS-induced colitis, and to a greater extent than M(IL4)-CD206low from the same individual. IL-10 production was increased in M(IL4)-CD206high-T-cell co-cultures. Having confirmed the prohealing effect of the human M(IL4), the predominant meta-cluster M(IL4)-CD206high was found to have superior anticolitic effect. Reduced numbers of M0-CD206high and M(IL4)-CD206high cells in some individuals with Crohn's disease suggest that their absence may contribute to more severe inflammation or reduced healing capacity.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"118 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345547","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}
Priya Hegde, Clayton Sandel, Alexander Schmidt, Stacey Lee, Janine Preble, C Stephen Foster, Stephen Anesi, Shilpa Kodati, Dimitrios Karamichos, Darren J Lee
{"title":"Saliva as a noninvasive diagnostic for ocular sarcoidosis.","authors":"Priya Hegde, Clayton Sandel, Alexander Schmidt, Stacey Lee, Janine Preble, C Stephen Foster, Stephen Anesi, Shilpa Kodati, Dimitrios Karamichos, Darren J Lee","doi":"10.1093/jleuko/qiag065","DOIUrl":"10.1093/jleuko/qiag065","url":null,"abstract":"<p><p>Sarcoidosis is a multi-organ granulomatous disorder that predominantly affects the eyes, lungs, and skin. Biopsy, the standard for a definitive sarcoidosis diagnosis, is often impractical for ocular sarcoidosis due to the delicate nature of the eye and risks associated with surgical procedures such as inflammation, infection, retinal detachment, and cataracts. Ocular sarcoidosis is typically treated with steroids and immunosuppressive medications. However, because infectious uveitis exhibits a similar clinical presentation as ocular sarcoidosis, there is an incipient risk of inappropriate treatment without a definitive diagnosis. Failing to prescribe immunosuppressive medications to patients with ocular sarcoidosis can lead to scarring and permanent blindness; conversely, prescribing this treatment to patients with infectious uveitis risks exacerbating the infection and associated pathologies. Saliva is an emerging diagnostic biofluid that is easy to collect, cost-effective, and well-tolerated by patients. Although saliva has been used to identify biomarkers for diseases like cancer and diabetes, its use in diagnosing ocular diseases remains limited. This review provides an overview of sarcoidosis and ocular sarcoidosis, the utility of saliva as a diagnostic tool, and a pilot experiment testing if saliva can be used to diagnose ocular sarcoidosis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13311565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016050","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}
{"title":"T cell exhaustion: next-generation target of autoimmune diseases?","authors":"Yuzhen Ouyang, Mengchuan Luo, Kailin Li, Kangzhi Chen, Zeyi Wen, Qian Zhou, Guanzhong Shi, Siyu Xu, Zhaohui Luo, Huan Yang","doi":"10.1093/jleuko/qiag052","DOIUrl":"10.1093/jleuko/qiag052","url":null,"abstract":"<p><p>Exhausted T cells (Tex), characterized by impaired cytotoxic function, play a detrimental role in anti-tumor and anti-infection immunity but represent promising therapeutic targets for autoimmune diseases. Persistent exposure to auto-antigens drives autoreactive CD8+ or CD4+T cells toward an exhausted-state, thereby mitigating excessive damage to healthy tissues. Inducing T cell exhaustion may offer a targeted approach to suppress pathological autoimmunity. In this review, we describe the markers, characteristics, and developmental phases of T cell exhaustion, discuss its close association with autoimmune diseases, and highlight Tex as a potential biomarker. We also summarize Tex-targeted therapeutic strategies, including inhibitory receptor activation, TCR overstimulation, and metabolic intervention, to provide insights for future treatments. The clinical translation gap of Tex-targeted therapy has also been proposed from stability, safety, and disease-specific considerations. Although challenges remain in areas such as antigen specificity and tenuous tolerance, therapies targeting Tex hold considerable potential to disrupt pathogenic circuits, realize disease remission, and reduce the risk of relapse in autoimmune diseases.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773849","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}
{"title":"Hardwired and rewired: Tissue macrophages in homeostasis and cancer.","authors":"Hesham Mohei, Donn A Van Deren, Malay Haldar","doi":"10.1093/jleuko/qiag046","DOIUrl":"10.1093/jleuko/qiag046","url":null,"abstract":"<p><p>Macrophages are highly heterogeneous innate immune cells that populate virtually all tissues, in which they acquire distinct phenotypes and homeostatic functions shaped by their local environment. Although these cells can arise from either embryonic precursors or circulating monocytes, their ultimate identity reflects an interplay between developmentally encoded transcriptional programs and tissue-derived extrinsic cues. Using selected tissue-resident macrophage subsets as examples, we highlight how environmental signals activate specialized transcriptional modules layered upon a conserved ontogenetic framework to generate the remarkable diversity of macrophage states. We further summarize tissue-specific roles of macrophages and briefly consider how these context-dependent programs influence cancer biology.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"118 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005503","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}
Heather Mathie, Laura Medina-Ruiz, Fabian Schuette, Heba Halawa, Zuzanna Pocalun, Elise Pitmon, John Cole, Marieke Pingen, Gerard J Graham
{"title":"Chemokine receptor expression defines a trajectory from monocytes to mature macrophages in the lung.","authors":"Heather Mathie, Laura Medina-Ruiz, Fabian Schuette, Heba Halawa, Zuzanna Pocalun, Elise Pitmon, John Cole, Marieke Pingen, Gerard J Graham","doi":"10.1093/jleuko/qiag059","DOIUrl":"10.1093/jleuko/qiag059","url":null,"abstract":"<p><p>CCR1, CCR2, and CCR5 direct recruitment of monocytes and macrophages in inflammation. However, the discrete role for each receptor in monocyte/macrophage biology remains poorly understood, with previous reports citing receptor redundancy. Using transcriptomic approaches to examine inflammatory chemokine receptor expression on lung interstitial macrophage populations, we demonstrate that interstitial macrophages can be divided into 3 distinct subsets, each of which express specific patterns of chemokine receptors, and that there are dynamic changes in chemokine receptor expression as macrophages differentiate from monocytes in the lung. Furthermore, macrophages expressing different combinations of chemokine receptors are transcriptionally distinct, suggesting nonredundant functions for CCR1, CCR2, and CCR5. Finally, we examined changes in macrophage chemokine receptor expression in vitro after treatment with varied Toll-like receptor ligands and show that CCR1 is specifically increased in response to bacterial but not viral ligands. Our data provide compelling evidence that macrophage chemokine receptor expression is not redundant, but rather is specific and malleable in response to discrete inflammatory stimuli.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13196878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838964","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}
{"title":"Withania somnifera extracts and withaferin A differentially regulate neutrophil pyroptosis, NETosis, and apoptosis.","authors":"Partha Sarathi Mondal, Apurwa Singhal, Ritvik Guru, Priyanka Kothari, Tulika Chandra, Anagha Ranade, Alok Kumar Srivastava, Manoj Kumar Barthwal, Madhu Dikshit, Sachin Kumar","doi":"10.1093/jleuko/qiag049","DOIUrl":"10.1093/jleuko/qiag049","url":null,"abstract":"<p><p>Neutrophils are short-lived, yet critical components of the innate immune system. These cells play crucial roles in host defense and inflammation. Their high turnover during inflammatory responses is often accompanied by inflammatory lytic cell death, such as NETosis and pyroptosis, which can amplify tissue damage. Thus, targeting neutrophil death pathways is an emerging therapeutic area. Withania somnifera (L.) Dunal (WS), a key Ayurvedic herb, shows immunomodulatory properties, but its effects on neutrophils remain underexplored. In this study, we investigated the impact of WS extracts and their major constituents, including withanolide A (WL), withanoside IV (WT), withanone (WO), and withaferin A (WFA), on the mechanisms of neutrophil death. Our findings reveal that WS extracts significantly attenuate interleukin-1β (IL-1β) release and pyroptotic cell death, with the alcoholic extract exhibiting greater efficacy than hydro-alcoholic and aqueous preparations. These effects are linked to the inhibition of NLRP3 inflammasome activation and caspase-1 signaling. Moreover, the alcoholic extract of WS suppressed phorbol 12-myristate 13-acetate (PMA)-induced NET formation, but did not affect ionomycin-induced NETosis. This selective inhibition was associated with a reduction in reactive oxygen species (ROS) generation, but had no effect on peptidyl arginine deiminase 4 (PAD4) activity. The WS alcoholic extract also conferred protection against neutrophil apoptosis, as evidenced by the downregulation of executioner caspase-7. Further analysis specified that WFA was primarily responsible for these effects. Together, these results provide novel insights into the role of WS and WFA in modulating neutrophil death pathways. These findings further highlighted the therapeutic potential of WS in inflammatory and neutrophil-mediated pathological conditions.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"118 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016074","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}