Journal of Immunology Research最新文献

{"title":"From Demyelination to Intervention: Natural Compounds as Emerging Therapeutic Targets in Multiple Sclerosis Neuroinflammation.","authors":"Zhiyong Long, Qianyue Yang, Yonghe Wu, Lifei Wan, Liuting Zeng, Lingyun Sun","doi":"10.1155/jimr/6333512","DOIUrl":"10.1155/jimr/6333512","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic immune-mediated inflammatory demyelinating disease of the central nervous system (CNS), characterized by multifocal lesions, axonal damage, and progressive neurological dysfunction, imposing a heavy burden on patients and healthcare systems. While T lymphocytes have long been regarded as central to MS pathogenesis, accumulating evidence underscores the pivotal role of B lymphocytes and dysregulated cytokine networks (e.g., Th17/IL-17 and NF-κB pathways) in driving disease initiation and progression. Despite advances in symptomatic management and disease-modifying therapies (DMTs), clinical interventions for MS remain constrained by severe side effects, drug dependency, and suboptimal long-term efficacy, highlighting an urgent unmet need for novel therapeutic strategies. Natural compounds (e.g., alkaloids, flavonoids, terpenoids, and polyphenols) have emerged as promising candidates owing to their inherent biocompatibility, favorable safety profiles, and multi-targeted regulatory effects on neuroinflammation. This review critically synthesizes and evaluates current evidence on the therapeutic potential of natural compounds in MS, with a focus on cross-compound class integration of core common pathways (e.g., NF-κB inhibition and Th17/Treg balance modulation) rather than isolated mechanism descriptions. We explicitly compare the strength of evidence across different natural compounds, clarifying which findings are well-substantiated versus preliminary. Notably, we emphasize the inherent limitations of experimental autoimmune encephalomyelitis (EAE) models in recapitulating human MS pathophysiology (e.g., interspecies immune divergence and disease heterogeneity) and integrate or at least reference relevant clinical/epidemiological evidence to enhance translational relevance. Finally, we outline key future perspectives, including the integration of natural products with existing DMTs, challenges in clinical trial design, and prospects of combination therapies, aiming to provide a directional framework for advancing natural compounds from preclinical exploration to actionable clinical therapeutic targets in MS and enhancing the translational impact of this field.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e6333512"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512651","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":"Myeloid-Derived Suppressor Cells: Immunoregulatory Roles and Therapeutic Prospects in Immune-Mediated Hematological Disorders.","authors":"Qi Liu, Kunpeng Zhang, Shun He, Xinru Jia, Jingjing Liu, Dijiong Wu, Baodong Ye","doi":"10.1155/jimr/5577070","DOIUrl":"10.1155/jimr/5577070","url":null,"abstract":"<p><p>Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that have been increasingly defined and characterized over the past two decades, known for their remarkable capacity to expand and exert immunosuppressive effects in various pathological contexts, such as malignancies, infections, and inflammatory diseases. Although MDSCs have attracted significant attention in tumor immunology, their multifaceted roles in immune-mediated hematological disorders remain comparatively understudied and less understood, especially in contrast to their well-documented functions in both solid and hematological malignancies. This review delves into the biological characteristics and functional mechanisms of MDSCs, as well as their dual immunomodulatory roles in various immune-mediated hematological disorders such as immune thrombocytopenia and aplastic anemia. Substantial evidence indicates that in these diseases, the expansion, recruitment, and function of MDSCs are significantly altered, with their levels closely correlated to disease activity. Based on these findings, we further explore the therapeutic potential of targeting MDSCs. Manipulating MDSCs offers a pioneering perspective for the development of next-generation immunotherapies, which holds promise for reshaping the current treatment landscape of immune-mediated hematological disorders.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e5577070"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433257","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":"Cold Atmospheric Plasma Enhances Fn14 Signaling in Hair Follicle Stem Cells, Thereby Promoting the Healing of Diabetic Skin Wounds in a Mouse Model.","authors":"Xiaoyan Zou, Lingling Peng, Mai Luo, Ziqing Qu, Guanglei Hu, Xiaoming Liu, Zhu Yan, Shruti Pokharel, Yumin Xia, Fangyan Jia","doi":"10.1155/jimr/9082774","DOIUrl":"10.1155/jimr/9082774","url":null,"abstract":"<p><p>The healing of diabetic skin wounds is often delayed due to cellular dysfunction and oxidative stress. Recently, cold atmospheric plasma (CAP) has shown promising efficacy in treating diabetic wounds; however, its exact mechanism remains unclear. The study aimed to investigate the effect of CAP on fibroblast growth factor-inducible 14 (Fn14) signaling-mediated hair follicle stem cell (HFSC) functionality, which may contribute to the healing of diabetic wounds. In vitro experiments were conducted to analyze the effect of CAP treatment on HFSC proliferation, cytokine production, and reactive oxygen species (ROS)-related protein expressions. Animal experiments were performed to verify the effect of CAP treatment on a mouse type 1 diabetic wound model. CAP enhanced both Fn14 expression and HFSC proliferation, accompanied by the activation of the Wnt/β-catenin signaling pathway. Expressions of Sirt1, Nrf2, hypoxia-inducible factor-1α, and Sox9, which were initially suppressed under high glucose conditions, were significantly restored upon CAP stimulation. Moreover, CAP-activated hydrogel promoted diabetic wound healing in this mouse model. Furthermore, inhibition of Fn14 abrogated the promotive effect of CAP intervention. Fn14 signaling is a key mediator, mechanistically linking CAP to HFSC activation and tissue repair. These findings provide a therapeutic blueprint for CAP-based regeneration of diabetic wounds.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e9082774"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838826","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":"CD39 Expression in Peripheral CD4+ T Lymphocytes Is Associated With Disease Activity in Patients With Systemic Lupus Erythematosus.","authors":"Hao Jin, Lu Tang","doi":"10.1155/jimr/6676375","DOIUrl":"10.1155/jimr/6676375","url":null,"abstract":"<p><strong>Objective: </strong>Regulatory T cells (Tregs) and CD4-positive T cells are crucial for the immunological control of systemic lupus erythematosus (SLE). As a crucial component of the adenosine metabolism pathway, CD39 influences the development and functionality of several immune system lymphocyte subsets, such as CD4-positive T cells and Tregs. The purpose of this study was to examine the connection between the activity of SLE disease and the numbers of Tregs and CD4-positive T lymphocytes, as well as the expression levels of the CD39 molecule on these cells.</p><p><strong>Methods: </strong>One hundred and eight SLE patients had peripheral blood drawn. The patients were split into two distinct categories: the SLE active group and the SLE low-activity group, depending on the illness activity. Using flow cytometry, the proportions and absolute numbers of CD4-positive T cells and Tregs, as well as the expression of CD39 on these cells, were measured. Their associations with SLE disease activity were examined. Last, CD39 was assessed as a possible biomarker for the activity of SLE illness.</p><p><strong>Results: </strong>Compared to the SLE low-activity group, the SLE active group's peripheral blood had a larger percentage and quantity of CD4-positive T cells. In contrast, it was discovered that the SLE active group had fewer Tregs overall, both in terms of percentage and quantity, than the SLE low-activity group. Compared to those in the SLE low-activity group, patients in the SLE active group exhibited noticeably greater levels of CD39 expression in both Tregs and CD4-positive T cells. Additionally, this study showed a favorable correlation between the percentage and absolute quantity of Tregs and the expression level of CD39 on Tregs. On the other hand, there is a negative correlation between the percentage and absolute quantity of CD4-positive T cells and the expression level of CD39 on these cells. Furthermore, CD39 is a possible biomarker that could help in the identification of SLE disease activity, according to receiver operating characteristic (ROC) curve research.</p><p><strong>Conclusion: </strong>According to this study, CD4-positive T cells' surface CD39 molecule serves a similar purpose to Tregs', namely immunological suppression. Therefore, a subpopulation of T cells with immunosuppressive properties is defined by CD4+CD39+ T lymphocytes, which may be a more accurate marker for differentiating disease activity in SLE.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e6676375"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433419","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":"RETRACTION: Anti-Inflammatory and Healing Activity of the Hydroalcoholic Fruit Extract of Solanum diploconos (Mart.) Bohs.","authors":"Journal Of Immunology Research","doi":"10.1155/jimr/9801373","DOIUrl":"10.1155/jimr/9801373","url":null,"abstract":"","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e9801373"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433263","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 Follicular Helper Cell Immune Signatures Associated With Disease Severity in Severe Fever With Thrombocytopenia Syndrome.","authors":"Danning Xu, Ting Wang, Wei Wei, Yun Wang, Rujia Chen, Renren Ouyang, Shiji Wu, Feng Wang, Hongyan Hou","doi":"10.1155/jimr/8984077","DOIUrl":"10.1155/jimr/8984077","url":null,"abstract":"<p><strong>Background: </strong>Severe fever with thrombocytopenia syndrome (SFTS) is marked by high case fatality and profound antiviral immune dysregulation, yet the clinical implications of changes in circulating T follicular helper (Tfh) cells remain unclear.</p><p><strong>Methods: </strong>We enrolled 79 patients with RT-PCR-confirmed SFTSV infection who were hospitalized from May to October 2023 and categorized them as acute-phase survivors (AS) or acute-phase deceased (AD). Frequencies of circulating Tfh subsets (Tfh1, Tfh2, Tfh17, and PD-1⁺ Tfh) were measured by flow cytometry, and plasma SFTSV RNA was quantified by RT-qPCR. Their relationships with clinical variables and prognosis were analyzed using correlation analysis, ROC analysis, Kaplan-Meier survival analysis, and forward-selection multivariable logistic regression.</p><p><strong>Results: </strong>Compared with survivors, patients in the AD group showed greater inflammatory activation, more pronounced coagulation disturbances, and higher plasma viral loads. While overall circulating Tfh frequencies were elevated in AD patients, subset profiling demonstrated a clear bias toward Tfh2 expansion together with contraction of Tfh1 and Tfh17 populations. Among these subsets, Tfh2 had the best discriminatory value for mortality (AUC = 0.724). Lower Tfh1 and Tfh17 frequencies were associated with poorer 28-day survival. Viral RNA levels were positively related to total Tfh and Tfh2 frequencies and negatively related to Tfh17. After adjustment for age, HLH status, and viral load, Tfh1 remained an independent correlate of acute-phase mortality.</p><p><strong>Conclusions: </strong>Acute SFTSV infection is associated with substantial remodeling of the circulating Tfh compartment. Expansion of Tfh2 alongside reduction of Tfh1 and Tfh17 was linked to heavier viral burden and worse clinical outcome. The independent association between lower Tfh1 frequency and mortality suggests that Tfh profiling may be useful for early risk assessment and offers mechanistic insight into defective humoral immunity in severe SFTS.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e8984077"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308196","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":"siRNA-Based Nanodrug Delivery Systems in the Treatment of Autoimmune Diseases.","authors":"Yi Liu, Zhihui Feng, Biao Zhang, Xueli Yang, Fei Yang, Guiya Lu, Chunhong Li, Chune Mo, Minglin Ou, Xianliang Hou","doi":"10.1155/jimr/2307551","DOIUrl":"10.1155/jimr/2307551","url":null,"abstract":"<p><p>Autoimmune diseases are chronic disorders with complex pathogenesis. Immune homeostasis disruption is closely associated with disease initiation and progression. Despite extensive research, the precise mechanisms underlying these diseases remain elusive. Conventional therapeutic approaches for autoimmune diseases primarily involve the administration of immunosuppressants, glucocorticoids, and monoclonal antibodies, each of which presents certain limitations. The emergence of RNA interference (RNAi) therapeutics has introduced a novel avenue for addressing these conditions. The development of an optimally engineered vector for RNAi drugs is anticipated to significantly enhance their clinical applicability. Nanomaterials, as promising drug carriers, offer robust support for RNAi therapeutics. This review summarizes recent advances and applications of nanodelivery systems for small interfering RNA (siRNA) therapeutics in autoimmune disease treatment. It also analyzes the challenges and future prospects of nanomaterial application in this field.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e2307551"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663855","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":"Integration of SFTSV Viral Load, Age, and Double-Negative B-Cells as Prognostic Biomarkers for Severe Fever With Thrombocytopenia Syndrome Outcomes.","authors":"Wei Wei, Qian Tai, Heng Liu, Rujia Chen, Yun Wang, Ting Wang, Renren Ouyang, Shiji Wu, Feng Wang, Hongyan Hou","doi":"10.1155/jimr/8554086","DOIUrl":"10.1155/jimr/8554086","url":null,"abstract":"<p><strong>Background: </strong>Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral illness with high mortality, yet early risk stratification remains challenging. Recent evidence suggests that B-cell dysregulation contributes to disease severity.</p><p><strong>Methods: </strong>A cohort of 168 patients with confirmed SFTS was retrospectively analyzed. Flow cytometry was used to quantify B-cell subsets in peripheral blood at admission. Laboratory markers, viral load, and B-cell phenotypes were evaluated for prognostic relevance using univariate and multivariate Cox regression analyses. Receiver operating characteristic (ROC) curves and nomogram models were employed to assess predictive value.</p><p><strong>Results: </strong>Deceased patients exhibited significantly higher viral loads, elevated proinflammatory cytokines (interleukin-6 (IL-6), IL-10, and tumor necrosis factor-alpha (TNF-α)), and markers of multiorgan dysfunction. Immunophenotyping revealed a reduction in naïve B-cells (IgD⁺CD27^-), alongside expansion of double negative B-cells (DNBs) (IgD^-CD27^-) in fatal cases. Furthermore, viral load was positively correlated with inflammatory cytokines and dysfunctional B-cell subsets, suggesting that impaired humoral immunity contributes to persistent hyperinflammation in severe SFTS. Multivariate Cox regression analysis identified higher viral load (HR = 2.193, p  < 0.001), older age (HR = 1.073, p  < 0.001), and increased proportion of DNBs (HR = 1.024, p = 0.035) as independent predictors of 28-day mortality. A combined prognostic model integrating these variables achieved excellent performance (AUC = 0.906, 95% CI: 0.814-0.967), significantly surpassing individual markers and enabling early identification of high-risk SFTS patients.</p><p><strong>Conclusion: </strong>This study demonstrates that integrating B-cell subset profiling with laboratory indicators significantly improves early prognostic assessment in SFTS. These findings provide insights into immune-pathological mechanisms and support timely risk stratification and intervention to reduce mortality.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e8554086"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433505","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":"The Traditional Chinese Medicine Compound Hezi Qingyou Formula Controls the MAPK Signaling Pathway for Alleviating Gastric Ulcer Induced by Acetic Acid in Rats.","authors":"Zhong Feng, Ruixia Wei, Junhao Tian, Hui Li, Haobo Chen, Yajie Hao, Meiyun Chen, Bingmei Su, Yuqian Lai, Mingjin Xun, Guimin Zhang, Meicun Yao","doi":"10.1155/jimr/2178079","DOIUrl":"10.1155/jimr/2178079","url":null,"abstract":"<p><p>In clinical practice, Hezi Qingyou Formula (HZQYF) has been observed to effectively alleviate clinical symptoms associated with gastri ulcers, though its precise mechanism of action remains unclear. To investigate the effects of HZQYF on gastric ulcers, we established a rat model of gastric ulcer and examined its impact on ulcer area, pathological changes, inflammatory cytokines, gastric repair factors, levels of T-superoxide dismutase (SOD), and malondialdehyde (MDA), as well as metabolites in gastric tissue and feces. The results demonstrated that HZQYF significantly reduced the gastric ulcer area and promoted gastric tissue repair in rats. It downregulated the phosphorylation of P-P38, P-JNK1/2, and ERK1/2 proteins in the mitogen-activated protein kinases (MAPKs) pathway, inhibited pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α), enhanced the expression of gastric repair factors including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), trefoil factor family 2 (TFF2), and prostaglandin E2 (PGE2), reduced MDA content, and increased the activity of the antioxidant enzyme T-SOD, thereby suppressing inflammatory responses and ameliorating gastric mucosal damage. Metabolomic studies revealed that HZQYF effectively normalized 40 metabolites in gastric tissue through four key metabolic pathways and 39 metabolites in feces through five key metabolic pathways. Notably, it regulated taurine and hypotaurine metabolism, as well as phenylalanine metabolism, restoring metabolite levels to normal and ameliorating metabolic disorders in diseased rats. In conclusion, HZQYF promotes the healing of experimental gastric ulcers in rats through anti-inflammatory effects, activation of gastric repair factors, and normalization of gastric tissue metabolites, suggesting its potential therapeutic role in the treatment of gastric ulcers.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e2178079"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433423","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":"Artesunate Alleviates Inflammatory Injury in Neonatal Acute Respiratory Distress Syndrome Through CCL5-Mediated Pyroptosis of M2 Macrophage Subsets.","authors":"Hai-Ran Ma, Yan-Mei Xie, Yu-Xuan Zhang, Chong-He Cui, Jing Liu","doi":"10.1155/jimr/7437447","DOIUrl":"10.1155/jimr/7437447","url":null,"abstract":"<p><p>Neonatal acute respiratory distress syndrome (NARDS) is a life-threatening respiratory disorder characterized by high mortality and significant long-term morbidity. Increasing evidence suggests that pyroptosis contributes to pulmonary tissue injury in ARDS. In this study, single-cell RNA sequencing (scRNA-seq) was utilized to investigate the molecular mechanisms underlying pyroptosis within the NARDS microenvironment. Our analysis identified chemokine (C-C motif) ligand (CCL5) expression in M2 macrophages as a potential regulator of pyroptosis associated with impaired tissue repair. Mechanistically, CCL5 was linked to the activation of the pyroptotic pathway through interactions with inflammasome components, promoting caspase-11-dependent gasdermin D (GSDMD) cleavage and interleukin-1β (IL-1β) release. Network pharmacology analysis identified artesunate, a clinically approved antimalarial drug, as a potential inhibitor of CCL5 expression in patients with NARDS. Functional validation showed that artesunate attenuated M2 macrophage pyroptosis, reduced pulmonary injury, and promoted tissue repair. Collectively, our findings identify CCL5 as a potential regulator of macrophage pyroptosis and support the therapeutic potential of artesunate for modulating pyroptosis-associated inflammation in NARDS. This study provides a mechanistic framework for the development of CCL5-targeted interventions and highlights the dual anti-inflammatory and pro-repair properties of artesunate in NARDS treatment.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e7437447"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678853","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}