Cell Death Discovery最新文献

{"title":"Sustained dysregulation of iron and glutathione homeostasis induces chronoferroptosis, a persistent ferroptotic adaptation in neuronal cells.","authors":"Nawab John Dar, David Soriano-Castell, Pamela Maher","doi":"10.1038/s41420-026-03208-6","DOIUrl":"10.1038/s41420-026-03208-6","url":null,"abstract":"<p><p>Although iron accumulates in brain regions impacted by neurodegenerative diseases such as Alzheimer's and Parkinson's, how chronic elevated iron levels contribute to neuronal dysfunction remains unclear. Here, we show that sustained iron overload, but not acute exposure, leads to a state of ferroptotic stress where nerve cells remain viable but become hypersensitive to oxidative injury. Retinoic acid-differentiated SH-SY5Y neuronal cells were exposed to acute (6-8 h) or chronic (9 days) iron loading to model transient versus prolonged age-related iron stress. While acute iron exposure produced minimal biochemical changes and did not sensitize cells to oxidative or ferroptotic challenges, chronic iron exposure induced ferritin upregulation, mitochondrial superoxide accumulation, suppression of GPX4 expression, elevated lipid peroxidation and loss of cellular glutathione (GSH). In addition, chronic but not acute GSH depletion by buthionine sulfoximine (BSO) recapitulated the iron-induced phenotype. Cells under chronic ferroptotic stress exhibited increased sensitivity not only to the ferroptosis inducer RSL-3 but also to hydrogen peroxide. Ferrostatin-1 significantly mitigated these effects suggesting that lipid peroxidation drives this state. Together, these findings demonstrate that, in contrast with acute exposure, chronic disruption of iron homeostasis with consequent GSH depletion remodels cellular redox homeostasis over time, inducing a state we term chronoferroptosis: a persistent ferroptotic adaptation characterized by coordinated alterations in iron-handling and antioxidant defense proteins that may represent early vulnerability to neurodegenerative pathology. Thus, these studies highlight the importance of sustained stress paradigms for modeling the progressive nature of neurodegenerative diseases. Graphical abstract illustrating how prolonged iron or BSO exposure drives a persistent ferroptotic stress state in RA differentiated SH-SY5Y cells. These cells were subjected to either acute exposure for 6-8 h or chronic exposure for 9 days. Acute iron or BSO treatment caused minimal biochemical changes and did not increase vulnerability to oxidative or ferroptotic challenges. In contrast, chronic exposure stimulated ferritin production, mitochondrial superoxide buildup, GSH depletion, reductions in GPX4 expression and increased lipid peroxidation without altering cell viability. However, these chronically stressed neuronal cells became markedly more sensitive to secondary stressors such as RSL-3 or hydrogen peroxide resulting in decreases in cell viability, whereas viability was not altered in acutely treated cells.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The multi-omics landscape of lung adenocarcinoma evolution: deciphering metabolic reprogramming-driven immune escape and its implications in combined therapy.","authors":"Na Liu, Guohu Han, Jing Jia, Minbin Chen","doi":"10.1038/s41420-026-03196-7","DOIUrl":"https://doi.org/10.1038/s41420-026-03196-7","url":null,"abstract":"<p><p>The progression of lung adenocarcinoma (LUAD) from pre-invasive lesions (atypical adenomatous hyperplasia/adenocarcinoma in situ) to invasive adenocarcinoma constitutes a complex, multi-dimensional, and dynamic process. While the genomic drivers underlying this transition have been extensively characterized, the mechanisms by which metabolic reprogramming remodels the tumor immune microenvironment to orchestrate immune escape remain a critical knowledge gap. Leveraging insights from multi-omics integration encompassing genomics, metabolomics, single-cell RNA sequencing, and spatial transcriptomics, this review systematically delineates the molecular mechanisms through which metabolic reprogramming acts as a pivotal driver of immune escape during LUAD evolution. We critically dissect the intricate metabolic-epigenetic-spatial-immune; specifically, we highlight the mechanism through which cancer cells impair immune effector function via nutrient deprivation and utilize oncometabolites to instigate epigenetic modifications, thereby imprinting an immunosuppressive phenotype at the genetic level. Furthermore, this review discusses the development of early-screening biomarkers based on metabolic signatures, as well as combination therapeutic strategies targeting dual metabolic-immune checkpoints. The aim is to provide a novel theoretical framework for improving clinical management and prognosis in patients with LUAD.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast adipogenesis restricts hemangioma growth through a PPARγ/Hippo-YAP/TAZ axis that promotes endothelial apoptosis and cell cycle arrest.","authors":"Sheng-Ming Qu, Bing Wang","doi":"10.1038/s41420-026-03176-x","DOIUrl":"10.1038/s41420-026-03176-x","url":null,"abstract":"<p><p>Infantile hemangioma (HEM) is the most common benign vascular tumor in infancy and is characterized by a unique progression pattern involving rapid proliferation followed by spontaneous involution. Increasing evidence suggests that the tumor microenvironment plays a critical role in regulating endothelial cell behavior during HEM development. In this study, we investigated how fibroblast (FB) phenotypic remodeling influences hemangioma endothelial cell (HemEC) function. Through single-cell RNA sequencing analysis, we identified extensive communication between FBs and ECs within HEM tissues. Functional experiments revealed that adipogenically differentiated FBs markedly suppressed HemEC proliferation, migration, invasion, and tube formation while promoting apoptosis. Transcriptomic analysis further demonstrated that this inhibitory effect was mediated by activation of the Hippo-YAP/TAZ signaling pathway in ECs. Mechanistically, adipogenic differentiation significantly upregulated PPARG expression in FBs, which in turn triggered Hippo pathway activation in ECs, leading to YAP/TAZ phosphorylation and nuclear exclusion. Importantly, PPARG silencing in FBs or pharmacological inhibition of the Hippo pathway reversed these effects. Collectively, our findings reveal a previously unrecognized microenvironmental regulatory mechanism in which PPARγ-driven fibroblast adipogenesis suppresses HEM progression through activation of the Hippo-YAP/TAZ pathway in endothelial cells. This study provides new insights into stromal-endothelial communication in HEM and suggests that the PPARγ-Hippo signaling axis may represent a potential therapeutic target. Proposed molecular mechanism by which PPARγ-mediated FB adipogenic differentiation regulates Hippo-YAP/TAZ signaling activity in HemECs. Note: Created in Biorender.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The IKKα-regulated microRNA miR-9-5p mediates lung cancer growth and invasiveness via CDH1/Wnt/β-catenin signalling.","authors":"Simoni Besta, Eugenia Roupakia, Zoi Kanaki, Giannis Vatsellas, Mark Samuels, Spyros Foutadakis, Maria Tokamani, Alessandro Barbon, Raphael Sandaltzopoulos, Dimitris C Kanellis, Jiri Bartek, Maria Hatziapostolou, Christos Polytarchou, Dimitris Thanos, Apostolos Klinakis, Evangelos Kolettas","doi":"10.1038/s41420-026-03195-8","DOIUrl":"10.1038/s41420-026-03195-8","url":null,"abstract":"<p><p>IKKα is a serine/threonine kinase that acts as a tumour suppressor in non-small cell lung cancer (NSCLC) in an NF-κΒ-independent manner, however, little is known about its downstream signalling pathways. To interrogate the IKKα signalling network in NSCLC, we investigated the impact of IKKα silencing on the miRNA expression profile of NSCLC cells. Nanostring miRNome analysis identified miR-9-5p, a known oncomir, as the top upregulated miRNA upon IKKα depletion. We show that overexpression of miR-9-5p in human lung cancer cells increases cell migration and invasion and promotes epithelial-to-mesenchymal cell transition (EMT) through loss of E-cadherin and activation of the Akt1/β-catenin pathway. In vivo tumour xenograft models show that overexpression of miR-9-5p promotes tumour growth and widespread transcriptomic reprogramming, altering the expression of genes related to EMT, apoptosis and NF-κB signalling. Overall, we show that miR-9-5p acts as an oncogenic effector upon IKKα loss, promoting tumour progression through EMT and Akt-1/GSK-3β/β-catenin pathway activation, leading to increased invasiveness and tumour growth.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoid-induced Leucine Zipper (GILZ) is a novel secreted protein by intestinal L-cells and is dysregulated during active ulcerative colitis.","authors":"Lucrezia Rosati, Giuseppe Leoncini, Luigi Cari, Maria Rosaria Sette, Martina Procaccini, Giuseppe Nocentini, Vincenzo Villanacci, Carlo Riccardi, Graziella Migliorati, Simona Ronchetti","doi":"10.1038/s41420-026-03204-w","DOIUrl":"10.1038/s41420-026-03204-w","url":null,"abstract":"<p><p>The Glucocorticoid-Induced Leucine Zipper (GILZ) is a key mediator of the anti-inflammatory effects of glucocorticoids, primarily within the immune system. Recent evidence has implicated GILZ as a secretive protein in goblet cells, with reduced expression linked to active Inflammatory Bowel Disease (IBD), suggesting a role in intestinal cell homeostasis. In this context, GILZ has been found also in enteroendocrine cells (EEC), but its role remained undefined. This study aimed at identifying GILZ-expressing EEC subtypes, dissecting how the secretive function is affected by inflammation in human ulcerative colitis (UC) and exploring its role in these cells. GILZ was predominantly expressed in glucagon-like-peptide-1 (GLP-1)-secreting L-cells, across all stages of EEC differentiation. GILZ was also expressed in serotonin (5HT)-producing enterochromaffin cells (EC), even though at low levels. Such an expression profile was supported by analysis of publicly available single-cell RNA sequencing datasets, identifying both EEC progenitors and mature subsets. Interestingly, confocal immunofluorescence localized GILZ to cytoplasmic granules partially co-staining with GLP-1-containing vesicles. Histological analysis of mucosal colonic biopsies revealed a global reduction in EEC during active UC as compared to healthy individuals and quiescent UC. Specifically, GILZ-expressing L-cells were significantly reduced in active UC and only partially restored in quiescent disease. In contrast, 5HT-producing EC cells were still reduced during active UC but fully recovered in quiescent disease. In vitro, NCI-H716 L-cell line-secreted products reduced IL-8 secretion in Caco2 epithelial cells, indicating an anti-inflammatory effect. This activity was attenuated following GILZ silencing. Interestingly, treatment with a recombinant TAT-GILZ protein directly diminished IL-8 in Caco2 cells. Collectively, our findings identify GILZ as a novel secretory product of L-cells with potential anti-inflammatory properties. Restoring GILZ secretion may represent a promising therapeutic strategy to mitigate chronic intestinal inflammation in UC.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HAAO‑derived quinolinic acid fuels FDPS‑dependent AR signaling and sensitizes prostate cancer to combination therapy.","authors":"Hongchang Zhang, Tingting Feng, Mengxue Lv, Zhurui Shao, Changhao Gong, Ruiying Chen, Ruojia Zhang, Yong Hou, Jinxiang Han, Di Wang, Lin Wang","doi":"10.1038/s41420-026-03203-x","DOIUrl":"10.1038/s41420-026-03203-x","url":null,"abstract":"<p><p>Emerging evidence highlights that metabolic reprogramming profoundly shapes the tumor microenvironment and immune evasion in prostate cancer. However, the functional role and mechanisms of tryptophan metabolism in prostate cancer progression remain unclear. Through single-cell transcriptomic analysis, we identified one tumor cell subtype characterized by high expression of 3-hydroxyanthranilate 3,4-dioxygenase (HAAO) and enhanced kynurenine pathway activity. This subpopulation leads to the accumulation of quinolinic acid (QA), a metabolic intermediate that could activate the mevalonate (MVA) pathway. Mechanistically, QA directly binds to and stabilizes farnesyl diphosphate synthase (FDPS), a key MVA pathway enzyme, thereby enhancing cholesterol biosynthesis and fueling androgen receptor (AR)-driven transcriptional programs. This HAAO/QA-FDPS axis establishes a metabolic crosstalk that links tryptophan catabolism to lipid metabolism, sustaining prostate tumor progression. Furthermore, an integrated prognostic model incorporating this pathway signatures outperforms other clinical variables alone, and HAAO-high tumors exhibit heightened sensitivity to combined inhibition of the kynurenine and AR pathways. Our study unveils a novel metabolic vulnerability in prostate cancer and provides a mechanistic rationale for targeting the HAAO/QA-FDPS axis for therapy.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deficiency of LIMA1 accelerates bladder cancer progression by disrupting PINK1/Parkin-mediated mitophagy.","authors":"Shuchen Zhao, Shuang Xu, Kai Cao, Yunfeng Shi, Tinchun Wu, Chengyue Wang, Shihui Li, Zhong Lv","doi":"10.1038/s41420-026-03136-5","DOIUrl":"10.1038/s41420-026-03136-5","url":null,"abstract":"<p><p>The LIM domain and actin-binding protein 1 (LIMA1), as a cytoskeletal-associated tumor suppressor, has not yet been clearly characterized in bladder cancer (BLCA). This study found that the cytoskeletal protein LIMA1 plays a key tumor-suppressing role in BLCA. Clinical analysis revealed that LIMA1 is significantly downregulated in tumor tissues and serum, with its low expression positively correlated with clinical stage, pathological grade, and recurrence risk, and predictive of poor prognosis. Functionally, LIMA1 knockout promotes tumor cell proliferation, migration, and invasion, and increases tumor volume by 1.8-fold in a mouse subcutaneous xenograft model. Mechanistically, database prediction and molecular docking confirmed that LIMA1 directly binds to PINK1, enhancing mitochondrial autophagy by activating the PINK1-Parkin pathway. The mitochondrial autophagy inducer uric acid A reverses the malignant phenotype caused by LIMA1 deficiency. In summary, this study reveals the inhibitory role of the LIMA1/PINK1/mitochondrial autophagy pathway in BLCA progression, providing a theoretical basis for novel therapeutic strategies targeting this pathway.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sympathetic signaling activation alleviated acute respiratory distress syndrome via the HDC/SLC7A11 axis in lipopolysaccharide-induced macrophages.","authors":"Xing Lv, Chenhao Jiang, Xu Zhang, Zhengqi Wu, Xuxia Wei, Yang Zhao, Jianhao Zhang, Xuegang Zhao, Lu Han, Yufeng He, Jianrong Liu, Yujun Zhang, Yuling An, Xiaomeng Yi, Yingcai Zhang, Xin Sui, Huimin Yi","doi":"10.1038/s41420-026-03173-0","DOIUrl":"10.1038/s41420-026-03173-0","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) represents a severe pulmonary condition characterized by excessive inflammation, wherein alveolar macrophages (AMs), pivotal components of the innate immune system, play a critical role in the pathogenesis of the disease. Despite its high morbidity and mortality, effective targeted therapies for ARDS remain unavailable. Norepinephrine (NE) is an endogenous neurotransmitter with immunomodulatory and anti-inflammatory properties, and has been reported to mitigate ARDS symptoms in sepsis models. While sympathetic signaling exerts protective effects, the underlying immunomodulatory mechanisms-especially those involving macrophages-remain poorly defined. Our in vitro experiments demonstrated that NE confers protection against LPS-induced injury in AMs by limiting lipid peroxidation, sustaining mitochondrial integrity, and upregulating antioxidant regulators SLC7A11 and GPX4, leading to improved cell viability. Mechanistically, the anti-ferroptotic effect of NE on LPS-treated AMs was significantly impaired by β2-adrenergic receptor (β2-AR) blockade or knockdown of histidine decarboxylase (HDC). Our in vivo experiments further demonstrated that salbutamol, a selective β2-AR agonist, upregulated SLC7A11 and GPX4 expression in septic mice and concurrently increased HDC expression in AMs. Furthermore, salbutamol alleviated lipid peroxidation, mitigated macrophage and lung tissue injury. These findings identify HDC/SLC7A11 as a potential axis involved in the neuroimmune regulation of ferroptosis in AMs, offering a potential therapeutic target for ARDS.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Drosophila nucleostemin 1 disrupts ribosomal protein homeostasis and rRNA processing to trigger apoptosis via the Xrp1/Irbp18 complex.","authors":"Xiuxiu Liu, Min Hou, Yuanyuan Zhang, Huan Liu, Xiaojiao Li, Yuanlin Su, Huiyuan Ding, Yanqin Gong, Qiao Liu, Yaoqin Gong, Gongping Sun","doi":"10.1038/s41420-026-03205-9","DOIUrl":"10.1038/s41420-026-03205-9","url":null,"abstract":"<p><p>Ribosome biogenesis, a process of producing ribosomes, plays an essential role in cell survival, proliferation and apoptosis. Nucleostemin (NS) is a conserved nucleolar protein highly expressed in proliferating cells but markedly reduced in differentiated cells. Previous studies on mammalian systems have shown that loss of NS triggers p53-dependent apoptosis and impairs ribosomal RNA (rRNA) processing. In this study, using the Drosophila wing imaginal disc, which is a proliferating epithelial tissue, we demonstrate that depletion of Ns1, the Drosophila homolog of mammalian NS, induces extensive p53-independent apoptosis and suppresses global translation. Notably, we find that Ns1 is required not only for rRNA processing but also for maintaining global ribosomal protein (RP) abundance. Loss of Ns1 leads to a reduction in 65 RPs. Furthermore, we show that Ns1 deficiency upregulates the Xrp1/Irbp18 complex, an effector mediating cellular response to ribosomal deficiency, which in turn activates JNK to trigger apoptosis and suppresses global translation through a mechanism independent of eIF2α phosphorylation and JNK. Our work establishes Ns1 as a critical regulator of ribosome biogenesis and cell survival in proliferating epithelia.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPR84 aggravates lung inflammation through activating ZBP1-PANoptosome mediated PANoptosis following IAV infection.","authors":"Hui Jiang, Youqin Zeng, Shijun Xu, Pengfei Wang, Shengjie You, Xiaobo Zhang, Hao Zhou","doi":"10.1038/s41420-026-03158-z","DOIUrl":"10.1038/s41420-026-03158-z","url":null,"abstract":"<p><p>Influenza virus-induced pneumonia (IVP) is a contagious lung disease marked by severe lung inflammation following viral infection and remains a significant public health concern due to its high mortality rate. G protein-coupled receptor 84 (GPR84) has been implicated in various inflammatory diseases, however, its role in influenza virus-induced lung inflammation remains poorly understood. In this study, using high-throughput screening, we found that Influenza A virus (IAV) infection markedly upregulates the expression of several G protein-coupled receptors, with GPR84 mRNA and protein levels being highly induced in the lungs of animal models during pneumonia. Mechanistically, GPR84 enhances ZBP1-PANoptosome mediated PANoptosis and exacerbates the release of inflammatory chemokines and danger associated molecular patterns (DAMPs). Notably, deletion of GPR84 attenuates influenza virus-induced PANoptosis, indicating that GPR84 participates in regulating lung inflammation and the pathogenesis of pneumonia during influenza infection. Overall, these findings demonstrate that GPR84 plays a central role in influenza virus-induced lung inflammation by promoting PANoptosis and the release of inflammatory mediators. Targeting GPR84 attenuates IAV-induced PANoptosis, highlighting its potential as a therapeutic target to mitigate the pathogenesis of influenza virus-induced pneumonia.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}