International immunopharmacology最新文献_第7页

Agmatine ameliorates poly(I:C)-induced lung injury through IL-10/STAT3-dependent reprogramming of macrophage inflammatory responses Agmatine通过IL-10/ stat3依赖性巨噬细胞炎症反应重编程改善poly（I:C）诱导的肺损伤

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-23 DOI: 10.1016/j.intimp.2026.116247

Zhen Sun , Xiaochang Zhang , Sha Liao , Zhe Zhou

The emerging field of immunometabolism posits that endogenous metabolites are pivotal regulators of immune responses, yet their therapeutic exploitation remains nascent. Investigating this paradigm in lung injury, we observed that agmatine, a decarboxylation product of L-arginine, was significantly depleted in poly(I:C)-induced murine lung injury and in a clinical cohort characterized by virus-associated pulmonary involvement, suggesting a potential association with lung pathology. In mice, exogenous agmatine supplementation ameliorated lung pathology and weight loss, effects that were contingent upon reprogramming of macrophage inflammatory responses. Mechanistically, agmatine exerts its anti-inflammatory effects through macrophage-specific mechanisms: it selectively inhibits macrophage-derived TNF-α and CXCL10 without affecting the NF-κB signaling pathway. Transcriptomic analysis of murine macrophages revealed that agmatine significantly upregulates IL-10 expression, and its protective effects were reversed using either IL-10R neutralizing antibody or macrophages from IL-10-deficient mice. In murine macrophages, further investigation confirmed that agmatine promotes STAT3 phosphorylation and nuclear translocation, while STAT3 knockdown partially abrogated its anti-inflammatory efficacy. Our findings position agmatine within the expanding realm of immunometabolic therapy, highlighting its potential as a therapeutic strategy for lung injury by harnessing an endogenous anti-inflammatory circuit.

新兴的免疫代谢领域认为内源性代谢物是免疫反应的关键调节因子，但其治疗开发仍处于初期阶段。在研究肺损伤的这种模式时，我们观察到，聚（I:C）诱导的小鼠肺损伤和以病毒相关肺受累为特征的临床队列中，l -精氨酸的脱羧产物agmatine显著减少，这表明它与肺病理有潜在的关联。在小鼠中，外源性胍丁氨酸补充剂改善了肺部病理和体重减轻，这些影响取决于巨噬细胞炎症反应的重编程。在机制上，agmatine通过巨噬细胞特异性机制发挥其抗炎作用：它选择性抑制巨噬细胞来源的TNF-α和CXCL10，而不影响NF-κB信号通路。小鼠巨噬细胞的转录组学分析显示，agmatine显著上调IL-10的表达，IL-10R中和抗体或IL-10缺陷小鼠的巨噬细胞均可逆转其保护作用。在小鼠巨噬细胞中，进一步的研究证实agmatine促进STAT3磷酸化和核易位，而STAT3敲低部分地消除了其抗炎作用。我们的研究结果将胍丁氨酸定位在免疫代谢治疗的不断扩大的领域，强调了其作为一种通过利用内源性抗炎回路治疗肺损伤的治疗策略的潜力。

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引用次数: 0

Role of reactive oxygen species in polycystic ovary syndrome: signalling pathways, mechanisms, and traditional Chinese medicine treatment strategies 活性氧在多囊卵巢综合征中的作用：信号通路、机制和中医治疗策略

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-23 DOI: 10.1016/j.intimp.2026.116251

Ziyi Wang , Shuyuan Liu , Mengyao Gao , Ying Shen , Miao Sun , Songli Hao

The biological role reactive oxygen species (ROS), both as byproduct of cellular respiration and as crucial secondary messengers, has been extensively acknowledged in scientific literature. Key ROS-generating enzymes and organelles, including mitochondria, NADPH oxidase, and the endoplasmic reticulum, have been found closely linked to the regulation of metabolic processes. An imbalance between oxidative and antioxidant systems, resulting from abnormal ROS production and leading to oxidative stress (OS), has been implicated as a significant pathogenic in a variety of diseases, such as polycystic ovary syndrome (PCOS). PCOS is a prevalent endocrine disorder that adversely affects reproductive health and metabolic homeostasis in women of reproductive age. This review provides a systematic examination of the three primary sources of ROS production, and explores the mechanisms through which excessive ROS production triggers the dysregulation of key signalling pathways. These pathways are central to the fundamental pathological features of PCOS, such as ovulatory dysfunction, obesity phenotype, insulin resistance, and hyperandrogenism, with a specific emphasis on the interactions within ROS signalling pathways. Grounded in the holistic regulation principles of Chinese medicine and targeting the core signalling pathway as the intervention focal point, we propose a comprehensive intervention strategy. This strategy incorporates natural compounds, herbal compounds, acupuncture, dietary supplements, and other therapeutic approaches, which will provide a new theoretical framework and research direction for enhancing the clinical management of PCOS.

活性氧（ROS）作为细胞呼吸的副产物和重要的次生信使，其生物学作用已在科学文献中得到广泛认可。关键的ros生成酶和细胞器，包括线粒体、NADPH氧化酶和内质网，已被发现与代谢过程的调节密切相关。氧化和抗氧化系统之间的不平衡，由ROS产生异常导致氧化应激（OS），已被认为是多种疾病的重要致病因素，如多囊卵巢综合征（PCOS）。多囊卵巢综合征是一种常见的内分泌紊乱，对育龄妇女的生殖健康和代谢稳态产生不利影响。这篇综述提供了ROS产生的三个主要来源的系统检查，并探讨了过量的ROS产生触发关键信号通路失调的机制。这些途径是PCOS基本病理特征的核心，如排卵功能障碍、肥胖表型、胰岛素抵抗和高雄激素症，特别强调ROS信号通路内的相互作用。基于中医整体调控原理，以核心信号通路为干预重点，提出综合干预策略。该策略结合了天然化合物、草药化合物、针灸、膳食补充剂等多种治疗手段，将为加强PCOS的临床管理提供新的理论框架和研究方向。

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引用次数: 0

A novel triazole derivative ameliorates ethanol-induced gastric ulcer via a NOS2-centered inhibition of the AGE-RAGE pathway 一种新型三唑衍生物通过以nos2为中心抑制AGE-RAGE通路改善乙醇诱导的胃溃疡

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-22 DOI: 10.1016/j.intimp.2026.116240

Cong Xie , Jiahui Yue , Wenying He , Changbin Yu

Ethanol-induced gastric ulcer, driven by intricate inflammatory and oxidative stress pathways, lacks optimally effective treatments. Utilizing an integrated approach combining network pharmacology and experimental validation in vivo using a mouse model and in vitro with gastric epithelial cells, this study elucidates the gastroprotective mechanism of the compound MPTA. Network pharmacology identified NOS2 as a central hub gene, guiding subsequent experimental investigation. In an ethanol-induced ulcer mouse model, MPTA administration dose-dependently ameliorated gastric mucosal damage, suppressed pro-inflammatory cytokines including TNF-α, IL-6, IL-1β and IL-8, elevated TGF-β and NO levels, and reduced oxidative stress; these protective effects were attenuated by a NOS2 inhibitor. Proteomic and molecular analyses demonstrated that MPTA downregulated the AGE-RAGE/NF-κB/p38 MAPK inflammatory pathway and activated the NRF2/HO-1/SOD2 antioxidant axis. In vitro, MPTA enhanced cell viability and migration while diminishing apoptosis and ROS accumulation in gastric epithelial cells, primarily through NOS2-centered regulation of the AGE-RAGE signaling pathway. We conclude that MPTA protects against ethanol-induced gastric injury by inhibiting NOS2 to mitigate inflammatory and oxidative stress via the AGE-RAGE pathway. This study unveils a novel gastroprotective mechanism centered on the downregulation of NOS2, underscoring its potential as a protective candidate for ethanol-induced gastric ulcer.

乙醇诱发的胃溃疡是由复杂的炎症和氧化应激途径驱动的，缺乏最佳有效的治疗方法。本研究采用网络药理学与体内小鼠模型及体外胃上皮细胞实验验证相结合的综合方法，阐明复方MPTA的胃保护机制。网络药理学鉴定NOS2为中心枢纽基因，指导后续实验研究。在乙醇诱导的溃疡小鼠模型中，MPTA剂量依赖性地改善了胃粘膜损伤，抑制了促炎细胞因子TNF-α、IL-6、IL-1β和IL-8，升高了TGF-β和NO水平，降低了氧化应激；这些保护作用被NOS2抑制剂减弱。蛋白质组学和分子分析表明，MPTA下调了AGE-RAGE/NF-κB/p38 MAPK炎症通路，激活了NRF2/HO-1/SOD2抗氧化轴。在体外，MPTA主要通过以nos2为中心调节AGE-RAGE信号通路，增强胃上皮细胞的活力和迁移，同时减少细胞凋亡和ROS积累。我们得出结论，MPTA通过AGE-RAGE通路抑制NOS2减轻炎症和氧化应激，从而保护胃免受乙醇诱导的损伤。这项研究揭示了一种以NOS2下调为中心的新的胃保护机制，强调了它作为乙醇性胃溃疡的保护性候选物的潜力。

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引用次数: 0

Antioxidant activity of 2-mercaptoethanol protects against CD8+ T cell overstimulation or accelerated exhaustion: evidence from an in vitro exhausted CD8+ T model and in vivo adoptive cell transfer 2-巯基乙醇的抗氧化活性可防止CD8+ T细胞过度刺激或加速衰竭：来自体外耗尽CD8+ T模型和体内过继细胞转移的证据

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-22 DOI: 10.1016/j.intimp.2026.116183

Muhammad Alaa Eldeen , Dalal Sulaiman Alshaya , Waleed K. Abdulsahib , Nuha Almulla , Mohamed A. Ali , Maha A. Aljumaa , Eman Fayad , Jawaher Alharthi , Hassan M. Otifi , Mohamed Alshehri , Reem S. Alazragi , Hesham M. Hassan

Background

CD8+ T cell exhaustion in the tumor microenvironment acts as a barrier to tumor immunotherapy development. Therefore, studying that cell in vitro and in vivo is essential for developing a successful cancer immunotherapeutic drug.

Methods

While repeated stimulation of CD8+ T cells in vitro is a must to acquire their exhaustion state, it is important to keep that to a limit that allows for exhaustion of the CD8+ T cells without accelerated cell death, so we can obtain enough exhausted CD8+ T cells to be studied. In the current study, we demonstrated the role of 2-mercaptoethanol (2-ME) as an essential media component by performing repeated CD8+ T cell stimulation with or without 2-ME.

Results

In the absence of 2-ME, CD8+ T cell suffers from overstimulation that allows for their accelerated death. Mechanistically, the absence of 2-ME elevates the oxidative stress on the CD8+ T cells, leading to a shift in their metabolic pathways by adopting lipid peroxidation, which hastens CD8+ T cells' terminal differentiation and over-activates the AKT-mTOR signaling pathway, and finally, cell death. These findings were reflected in our in vivo experiment, where adoptive transfer of antigen-specific CD8+ T cells that have been in vitro activated without 2-ME experienced a lower tumor infiltration frequency and diminished stemness characteristics and effector functions.

Conclusion

Our study confirms the importance of 2-ME as a media component for CD8+ T cells stimulation and supports the potential of antioxidant agents to be used with immunotherapeutic agents to generate enhanced effects.

肿瘤微环境中的cd8 + T细胞耗竭是肿瘤免疫治疗发展的障碍。因此，在体外和体内研究该细胞对于开发成功的癌症免疫治疗药物至关重要。方法虽然体外反复刺激CD8+ T细胞是获得其衰竭状态的必要条件，但重要的是要保持在一个限度内，允许CD8+ T细胞的衰竭而不加速细胞死亡，因此我们可以获得足够的CD8+ T细胞进行研究。在目前的研究中，我们通过使用或不使用2-ME对CD8+ T细胞进行重复刺激，证明了2-巯基乙醇（2-ME）作为一种重要的培养基成分的作用。结果在缺乏2-ME的情况下，CD8+ T细胞受到过度刺激，导致其加速死亡。机制上，2-ME的缺失会升高CD8+ T细胞的氧化应激，导致其代谢途径发生脂质过氧化改变，加速CD8+ T细胞的终末分化，过度激活AKT-mTOR信号通路，最终导致细胞死亡。这些发现在我们的体内实验中得到了反映，在没有2-ME的体外激活的抗原特异性CD8+ T细胞的过继转移经历了较低的肿瘤浸润频率和降低的干性特征和效应功能。结论我们的研究证实了2-ME作为刺激CD8+ T细胞的媒介成分的重要性，并支持抗氧化剂与免疫治疗剂联合使用以产生增强效果的潜力。

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引用次数: 0

Ginsenoside Rg1 ameliorates depression-like behaviors in mice by inhibiting astrocyte pyroptosis via Cx43-dependent restoration of mitophagy flux 人参皂苷Rg1通过cx43依赖性修复线粒体自噬通量抑制星形细胞凋亡，改善小鼠抑郁样行为。

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-22 DOI: 10.1016/j.intimp.2026.116243

Zan Xing , Xin-Mu Li , Yuan-Chun Wang , Peng-Yu Chen , Xue-Ying Yang , Hui-Qin Wang , Meng Zhang , Ai-Ping Chen , Shi-Feng Chu , Zhen-Zhen Wang , Nai-Hong Chen

Background

Ginsenoside Rg1 (GRg1), a principal neuroactive constituent of ginseng, has demonstrated promising antidepressant potential. Beyond its well-documented roles in mitigating oxidative stress, suppressing neuroinflammation, and protecting mitochondrial function, our study further demonstrates that GRg1 exerts its protective effects on the organism by upregulating the expression of connexin 43 (Cx43) in astrocytes. However, it remains unknown whether Cx43 mediates the antidepressant effects of GRg1 by regulating astrocyte pyroptosis.

Objective

This study aimed to elucidate the role of the Cx43-mitophagy-pyroptosis axis in the antidepressant mechanism of GRg1.

Methods

The model of depression was established using an 8-week chronic unpredictable stress (CUS). The optimal therapeutic dose of GRg1 was determined in vivo. Subsequently, we employed Western blotting, immunofluorescence, and fMRI to assess the effects of GRg1 on Cx43 expression and its protective effects on astrocytes. The causal role of Cx43 was verified using Cx43^flox/flox mice. Furthermore, we used corticosterone (CORT) to stimulate primary mouse astrocytes and conducted in vitro studies on the relationship between the “Cx43-mitophagy-pyroptosis” pathway and depression.

Conclusion

GRg1 exerts its antidepressant effects by upregulating Cx43 expression, which restores mitophagy flux and facilitates the clearance of damaged mitochondria. This process, in turn, suppresses NLRP3 inflammasome activation and subsequent GSDMD-N-mediated astrocyte pyroptosis.

背景：人参皂苷Rg1 （GRg1）是人参的主要神经活性成分，具有良好的抗抑郁作用。除了其在减轻氧化应激、抑制神经炎症和保护线粒体功能方面的作用外，我们的研究进一步表明，GRg1通过上调星形胶质细胞中连接蛋白43 （Cx43）的表达来发挥其对生物体的保护作用。然而，Cx43是否通过调节星形细胞焦亡介导GRg1的抗抑郁作用尚不清楚。目的：本研究旨在阐明Cx43-mitophagy-pyroptosis轴在GRg1抗抑郁机制中的作用。方法：采用8周慢性不可预测应激（CUS）模型建立抑郁模型。在体内确定GRg1的最佳治疗剂量。随后，我们采用Western blotting、免疫荧光和fMRI来评估GRg1对Cx43表达的影响及其对星形胶质细胞的保护作用。使用Cx43flox/flox小鼠验证了Cx43的因果作用。此外，我们使用皮质酮（CORT）刺激小鼠原代星形胶质细胞，并对“Cx43-mitophagy-pyroptosis”通路与抑郁症的关系进行了体外研究。结论：GRg1通过上调Cx43表达发挥抗抑郁作用，恢复线粒体自噬通量，促进受损线粒体的清除。这一过程反过来又抑制NLRP3炎性体激活和随后gsdmd - n介导的星形细胞焦亡。

{"title":"Ginsenoside Rg1 ameliorates depression-like behaviors in mice by inhibiting astrocyte pyroptosis via Cx43-dependent restoration of mitophagy flux","authors":"Zan Xing , Xin-Mu Li , Yuan-Chun Wang , Peng-Yu Chen , Xue-Ying Yang , Hui-Qin Wang , Meng Zhang , Ai-Ping Chen , Shi-Feng Chu , Zhen-Zhen Wang , Nai-Hong Chen","doi":"10.1016/j.intimp.2026.116243","DOIUrl":"10.1016/j.intimp.2026.116243","url":null,"abstract":"<div><h3>Background</h3><div>Ginsenoside Rg1 (GRg1), a principal neuroactive constituent of ginseng, has demonstrated promising antidepressant potential. Beyond its well-documented roles in mitigating oxidative stress, suppressing neuroinflammation, and protecting mitochondrial function, our study further demonstrates that GRg1 exerts its protective effects on the organism by upregulating the expression of connexin 43 (Cx43) in astrocytes. However, it remains unknown whether Cx43 mediates the antidepressant effects of GRg1 by regulating astrocyte pyroptosis.</div></div><div><h3>Objective</h3><div>This study aimed to elucidate the role of the Cx43-mitophagy-pyroptosis axis in the antidepressant mechanism of GRg1.</div></div><div><h3>Methods</h3><div>The model of depression was established using an 8-week chronic unpredictable stress (CUS). The optimal therapeutic dose of GRg1 was determined in vivo. Subsequently, we employed Western blotting, immunofluorescence, and fMRI to assess the effects of GRg1 on Cx43 expression and its protective effects on astrocytes. The causal role of Cx43 was verified using Cx43<sup>flox/flox</sup> mice. Furthermore, we used corticosterone (CORT) to stimulate primary mouse astrocytes and conducted in vitro studies on the relationship between the “Cx43-mitophagy-pyroptosis” pathway and depression.</div></div><div><h3>Conclusion</h3><div>GRg1 exerts its antidepressant effects by upregulating Cx43 expression, which restores mitophagy flux and facilitates the clearance of damaged mitochondria. This process, in turn, suppresses NLRP3 inflammasome activation and subsequent GSDMD-N-mediated astrocyte pyroptosis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"172 ","pages":"Article 116243"},"PeriodicalIF":4.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Recent research progress in structural optimization and cancer treatment of novel selective FGFR inhibitors (2020–2025) 新型选择性FGFR抑制剂结构优化与肿瘤治疗研究进展（2020-2025）

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-22 DOI: 10.1016/j.intimp.2026.116249

Rongfei Liu , Jinghui Qi , Yue Liu , Mingyue Hou , Mingyu Zhang , Xuan An , Jinxing Hu

Abnormalities in protein tyrosine kinases (PTKs) are one of the primary drivers of cancer. As a receptor subfamily, fibroblast growth factor receptors (FGFRs) comprise four subtypes—FGFR1 to FGFR4. Their abnormal intracellular expression is a significant cause of tumorigenesis, making FGFRs key therapeutic targets in cancer treatment. This paper primarily summarizes the latest research advances in FGFR inhibitors, aiming to provide insights for future design and synthesis studies of FGFR inhibitors.

蛋白酪氨酸激酶（PTKs）的异常是癌症的主要驱动因素之一。作为一个受体亚家族，成纤维细胞生长因子受体（FGFRs）包括四种亚型- fgfr1至FGFR4。它们在细胞内的异常表达是肿瘤发生的重要原因，使FGFRs成为癌症治疗的关键治疗靶点。本文主要综述了FGFR抑制剂的最新研究进展，旨在为未来FGFR抑制剂的设计和合成研究提供参考。

引用次数: 0

Pterostilbene ameliorates pulmonary fibrogenesis and inflammation targeting IL-23/ATP6V0D2 pathway: remodel local microenvironment of alveolar epithelial cells and fibroblasts 紫檀芪靶向IL-23/ATP6V0D2通路改善肺纤维化和炎症：重塑肺泡上皮细胞和成纤维细胞的局部微环境

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-22 DOI: 10.1016/j.intimp.2026.116256

Jia-Yi Dou, Chen-Yu Wang, Sai-Hu Liu, Chong Gao, Shuang Zheng, Li-Hua Lian, Zhen-Yu Cui, Ji-Xing Nan, Yan-Ling Wu

Pterostilbene (PTE) is a natural stilbene compound abundantly found in various small berries such as blueberry and grape, and exhibits multiple health promoting potentials and excellent pharmacological activities, especially antioxidant and anti-inflammatory activities. This study explored the protective effects of PTE on pulmonary fibrogenesis and inflammation and its underlying mechanisms. TGF-β-stimulated BEAS-2B or primary lung fibroblasts (LFs) were cultured with PTE or pirfenidone (PFD). Mice were received intratracheal instillation of bleomycin (BLM) and administered PTE or PFD. IL-23/ATP6V₀D₂-deficient BEAS-2B were treated with TGF-β or PTE. Primary LFs were stimulated with conditioned medium from TGF-β-primed RLE-6TN (CM) and treated with PTE. In vitro, PTE inhibited TGF-β-induced BEAS-2B cell migration, extracellular matrix (ECM) deposition, epithelial-mesenchymal transition (EMT) and inflammation. In BLM-induced mice, PTE reduced lung index and IL-1β levels in BALF, and improved histopathological changes. PTE inhibited BLM-induced fibrogenesis, EMT, inflammation and immune cell infiltration through blocking IL-23 and activating ATP6V₀D₂. In TGF-β-induced BEAS-2B, PTE decreased IL-23, increased ATP6V₀D₂ and ATP levels, and disrupted the interaction between IL-23 and ATP6V₀D₂. In IL-23-deficient BEAS-2B, PTE further elevated ATP6V₀D₂ and decreased α-SMA, Vimentin and IL-1β expressions. ATP6V₀D₂ deficiency attenuated the anti-fibrotic and anti-inflammatory effects of PTE in TGF-β-induced BEAS-2B. PTE also inhibited fibrogenesis, EMT, and inflammation in activated-primary LFs and blocked CM-triggered primary LFs activation by regulating IL-23-ATP6V₀D₂ axis. In conclusion, PTE ameliorated pulmonary fibrosis targeting IL-23/ATP6V₀D₂ pathway, especially remodeling the local microenvironment of alveolar epithelial cells and fibroblasts, which might be a novel therapeutic strategy against pulmonary fibrosis.

紫檀芪（PTE）是一种富含蓝莓、葡萄等多种小型浆果的天然芪类化合物，具有多种促进健康的潜力和良好的药理活性，尤其是抗氧化和抗炎活性。本研究探讨PTE对肺纤维化和炎症的保护作用及其机制。用PTE或吡非尼酮（PFD）培养TGF-β刺激的BEAS-2B或原代肺成纤维细胞（LFs）。小鼠气管内滴注博来霉素（BLM）并给予PTE或PFD。IL-23/ atp6v0d2缺陷的BEAS-2B分别用TGF-β或PTE处理，原代LFs用TGF-β引发的RLE-6TN （CM）条件培养基刺激，再用PTE处理，PTE在体外抑制TGF-β诱导的BEAS-2B细胞迁移、细胞外基质（ECM）沉积、上皮-间质转化（EMT）和炎症反应。在blm诱导的小鼠中，PTE降低了肺指数和BALF中IL-1β的水平，并改善了组织病理学改变。PTE通过阻断IL-23和激活ATP6V0D2，抑制blm诱导的纤维形成、EMT、炎症和免疫细胞浸润。在TGF-β诱导的BEAS-2B中，PTE降低IL-23，升高ATP6V0D2和ATP水平，破坏IL-23与ATP6V0D2的相互作用。在il -23缺失的BEAS-2B中，PTE进一步升高了ATP6V0D2，降低了α-SMA、Vimentin和IL-1β的表达。ATP6V0D2缺乏可减弱PTE在TGF-β诱导的BEAS-2B中的抗纤维化和抗炎作用。PTE还通过调节IL-23-ATP6V0D2轴抑制激活的原发性LFs的纤维化、EMT和炎症，并阻断cm触发的原发性LFs的激活。综上所述，PTE靶向IL-23/ATP6V0D2通路改善肺纤维化，特别是重塑肺泡上皮细胞和成纤维细胞的局部微环境，可能是一种新的肺纤维化治疗策略。

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引用次数: 0

Rutin ameliorates hepatic ischemia-reperfusion injury by targeting CD36 to suppress hepatocyte ferroptosis 芦丁通过靶向CD36抑制肝细胞铁凋亡改善肝缺血再灌注损伤

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-22 DOI: 10.1016/j.intimp.2026.116231

Zhenlong Liu , Miaomiao Wang , Liangyun Li , Wenmei Zhang , Wenna Meng , Chengjiang Cao , Hehang Song , Xue Fang , Yan Zhu , Ming Yang , Changlin Du , Yuan Zhang , Cheng Huang , Taotao Ma , Jun Li

Liver transplantation, the only curative option for end-stage liver disease, is limited by ischemia-reperfusion injury, with hepatocyte ferroptosis as a key pathogenic mechanism. CD36, a fatty acid translocase, drives the progression of multiple liver diseases. Yet, its role in hepatic ischemia-reperfusion injury (HIRI) and ferroptosis remains unclear. In this study, we generated full and hepatocyte-specific CD36 knockout mice to investigate its impact on HIRI. A significant upregulation of CD36 was observed in livers following ischemia-reperfusion (I/R) injury and in primary hepatocytes after hypoxia-reoxygenation (H/R). CD36 knockout alleviated liver injury and ferroptosis in HIRI models. In vitro, CD36 silencing suppressed H/R induced ferroptosis. Furthermore, our results establish rutin, a flavonoid derived from Gardenia, as a novel inhibitor of hepatocyte CD36 that alleviates HIRI. Mechanistically, CD36 regulates fatty acid binding protein 5 (FABP5) to reprogram lipid metabolism and drive ferroptosis in HIRI. Additionally, Rutin suppresses CD36 transcription through the stabilization of hepatocyte nuclear factor 4 α (HNF4α). Our findings demonstrate that CD36 exacerbates HIRI by regulating FABP5-mediated lipid metabolism and ferroptosis, while rutin exerts protective effects via CD36 inhibition. These results highlight the therapeutic potential of rutin for HIRI and identify the CD36/FABP5 axis as a novel target for intervention.

肝移植是终末期肝病的唯一治疗选择，受缺血再灌注损伤的限制，肝细胞铁凋亡是一个关键的致病机制。CD36，一种脂肪酸转位酶，驱动多种肝脏疾病的进展。然而，其在肝缺血再灌注损伤（HIRI）和铁下垂中的作用尚不清楚。在这项研究中，我们产生了完整的和肝细胞特异性CD36敲除小鼠来研究其对HIRI的影响。在缺血再灌注（I/R）损伤后的肝脏和缺氧再氧化（H/R）后的原代肝细胞中观察到CD36的显著上调。敲除CD36可减轻HIRI模型的肝损伤和铁下垂。体外，CD36沉默可抑制H/R诱导的铁下垂。此外，我们的研究结果表明，从栀子花中提取的黄酮类化合物芦丁是一种新型的肝细胞CD36抑制剂，可减轻HIRI。在机制上，CD36调节脂肪酸结合蛋白5 （FABP5）重编程脂质代谢并驱动HIRI中的铁下垂。此外，芦丁通过稳定肝细胞核因子4α (HNF4α)抑制CD36转录。我们的研究结果表明，CD36通过调节fabp5介导的脂质代谢和铁下沉而加重HIRI，而芦丁通过抑制CD36发挥保护作用。这些结果突出了芦丁对HIRI的治疗潜力，并确定了CD36/FABP5轴作为干预的新靶点。

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引用次数: 0

Lactiplantibacillus plantarum K4–9 strain stimulates antitumor immune responses through the activation of dendritic cells and CD8+ T cells 植物乳杆菌K4-9菌株通过激活树突状细胞和CD8+ T细胞刺激抗肿瘤免疫反应

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-22 DOI: 10.1016/j.intimp.2026.116244

Haruka Aso , Akihiro Masaki , Fumie Niitsuma , Hiroka Sasahara , Hyebin Jeong , Katsunori Endo , Taiga Yunoue , Junya Ohtake , Hidemitsu Kitamura , Sachi Tanaka

Activated dendritic cells (DCs) present tumor antigens to T cells, while CD8⁺ T cells induce apoptosis in cancer cells through the production of interferon (IFN)-γ and Granzyme B. Immune cells expressing chemokine receptors migrate to tumor sites in response to chemokines secreted by cancer cells. In our previous study, we demonstrated that Lactiplantibacillus plantarum K4–9 (K4–9), isolated from nozawana pickles, strongly promotes IFN-γ production. However, the detailed mechanisms underlying its antitumor effects remain unclear. This study aimed to elucidate the antitumor mechanisms of K4–9, particularly its involvement with DCs and CD8⁺ T cells. Oral administration of K4–9 increased the proportion of DCs in mouse spleen cells and upregulated the expression of activation markers CD40 and CD86 on DCs. Additionally, CD8⁺ T cells derived from the spleen cells of K4–9-administered mice exhibited increased mRNA expression levels of IFN-γ and Granzyme B. Administration of K4–9 also enhanced cytotoxic activity against B16F10 melanoma cells. Analysis of chemokine receptor expression revealed elevated CCR7 expression in DCs and increased CXCR3 expression in CD8⁺ T cells. Oral administration of K4–9 suppressed metastatic tumor formation in a mouse liver metastasis model using B16F10 cells. These results suggest that K4–9 exerts antitumor effects by promoting DC activation and enhancing CD8⁺ T cell responses. K4–9 holds promise as a functional food ingredient with potential antitumor properties.

激活的树突状细胞（dc）将肿瘤抗原呈递给T细胞，而CD8+ T细胞通过产生干扰素(IFN)-γ和颗粒酶b诱导癌细胞凋亡。表达趋化因子受体的免疫细胞根据癌细胞分泌的趋化因子迁移到肿瘤部位。在我们之前的研究中，我们证明了从野泽酸菜中分离的植物乳杆菌K4-9 （K4-9）强烈促进IFN-γ的产生。然而，其抗肿瘤作用的具体机制尚不清楚。本研究旨在阐明K4-9的抗肿瘤机制，特别是其与dc和CD8+ T细胞的关系。口服K4-9可增加小鼠脾细胞中dc的比例，上调dc上活化标志物CD40和CD86的表达。此外，来自K4-9给药小鼠脾脏细胞的CD8+ T细胞显示IFN-γ和颗粒酶b mRNA表达水平升高。K4-9的给药也增强了对B16F10黑色素瘤细胞的细胞毒活性。趋化因子受体表达分析显示dc中CCR7表达升高，CD8+ T细胞中CXCR3表达升高。口服K4-9抑制B16F10细胞小鼠肝转移模型中转移瘤的形成。这些结果表明K4-9通过促进DC活化和增强CD8+ T细胞反应发挥抗肿瘤作用。K4-9有望成为一种具有潜在抗肿瘤特性的功能性食品成分。

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引用次数: 0

Corrigendum to “Biodegradable Hypocrellin B nanoparticles coated with neutrophil membranes for hepatocellular carcinoma photodynamics therapy effectively via JUNB/ROS signaling” [Int. Immunopharmacol. 99 (2021) 107624] “中性粒细胞膜包裹的可生物降解Hypocrellin B纳米颗粒通过JUNB/ROS信号有效地用于肝癌光动力学治疗”的更正[j]。免疫药物，99 (2021)107624 [j]。

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-21 DOI: 10.1016/j.intimp.2026.116188

Zhiqiang Zhang , Dan Li , Yiming Cao , Yupeng Wang , Feixia Wang , Feng Zhang , Shizhong Zheng

引用次数: 0