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iMetAct: An integrated systematic inference of metabolic activity for dissecting tumor metabolic preference and tumor-immune microenvironment.
IF 7.5 1区 生物学
Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-06 DOI: 10.1016/j.celrep.2025.115375
Binxian Wang, Chao Huang, Xuan Liu, Zhenni Liu, Yilei Zhang, Wei Zhao, Qiuran Xu, Ping-Chih Ho, Zhengtao Xiao
{"title":"iMetAct: An integrated systematic inference of metabolic activity for dissecting tumor metabolic preference and tumor-immune microenvironment.","authors":"Binxian Wang, Chao Huang, Xuan Liu, Zhenni Liu, Yilei Zhang, Wei Zhao, Qiuran Xu, Ping-Chih Ho, Zhengtao Xiao","doi":"10.1016/j.celrep.2025.115375","DOIUrl":"10.1016/j.celrep.2025.115375","url":null,"abstract":"<p><p>Metabolic enzymes play a central role in cancer metabolic reprogramming, and their dysregulation creates vulnerabilities that can be exploited for therapy. However, accurately measuring metabolic enzyme activity in a high-throughput manner remains challenging due to the complex, multi-layered regulatory mechanisms involved. Here, we present iMetAct, a framework that integrates metabolic-transcription networks with an information propagation strategy to infer enzyme activity from gene expression data. iMetAct outperforms expression-based methods in predicting metabolite conversion rates by accounting for the effects of post-translational modifications. With iMetAct, we identify clinically significant subtypes of hepatocellular carcinoma with distinct metabolic preferences driven by dysregulated enzymes and metabolic regulators acting at both the transcriptional and non-transcriptional levels. Moreover, applying iMetAct to single-cell RNA sequencing data allows for the exploration of cancer cell metabolism and its interplay with immune regulation in the tumor microenvironment. An accompanying online platform further facilitates tumor metabolic analysis, patient stratification, and immune microenvironment characterization.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115375"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Modular mechanisms of immune priming and growth inhibition mediated by plant effector-triggered immunity.
IF 7.5 1区 生物学
Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-08 DOI: 10.1016/j.celrep.2025.115394
Himanshu Chhillar, Hoang Hung Nguyen, Pei-Min Yeh, Jonathan D G Jones, Pingtao Ding
{"title":"Modular mechanisms of immune priming and growth inhibition mediated by plant effector-triggered immunity.","authors":"Himanshu Chhillar, Hoang Hung Nguyen, Pei-Min Yeh, Jonathan D G Jones, Pingtao Ding","doi":"10.1016/j.celrep.2025.115394","DOIUrl":"10.1016/j.celrep.2025.115394","url":null,"abstract":"<p><p>Excessive activation of effector-triggered immunity (ETI) in plants inhibits plant growth and activates cell death. ETI mediated by intracellular Toll/interleukin-1 receptor/resistance protein (TIR) nucleotide-binding, leucine-rich repeat receptors (NLRs) involves two partially redundant signaling nodes in Arabidopsis, ENHANCED DISEASE SUSCEPTIBILITY 1-PHYTOALEXIN DEFICIENT 4-ACTIVATED DISEASE RESISTANCE 1 (EDS1-PAD4-ADR1) and EDS1-SENESCENCE-ASSOCIATED GENE 101-N REQUIREMENT GENE 1 (EDS1-SAG101-NRG1). Genetic and transcriptomic analyses show that EDS1-PAD4-ADR1 primarily enhances immune component abundance and is critical for limiting pathogen growth, whereas EDS1-SAG101-NRG1 mainly activates the hypersensitive response (HR) cell death but is dispensable for immune priming. This study enhances our understanding of the distinct contributions of these two signaling modules to ETI and suggests molecular principles and potential strategies for improving disease resistance in crops without compromising yield.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115394"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Piezo1 regulates colon stem cells to maintain epithelial homeostasis through SCD1-Wnt-β-catenin and programming fatty acid metabolism.
IF 7.5 1区 生物学
Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-12 DOI: 10.1016/j.celrep.2025.115400
Feifei Fang, Gangping Li, Xueyan Li, Jiandi Wu, Ying Liu, Haoren Xin, Zhe Wang, Jianhua Fang, Yudong Jiang, Wei Qian, Xiaohua Hou, Jun Song
{"title":"Piezo1 regulates colon stem cells to maintain epithelial homeostasis through SCD1-Wnt-β-catenin and programming fatty acid metabolism.","authors":"Feifei Fang, Gangping Li, Xueyan Li, Jiandi Wu, Ying Liu, Haoren Xin, Zhe Wang, Jianhua Fang, Yudong Jiang, Wei Qian, Xiaohua Hou, Jun Song","doi":"10.1016/j.celrep.2025.115400","DOIUrl":"10.1016/j.celrep.2025.115400","url":null,"abstract":"<p><p>Piezo1, which maintains the integrity and function of the intestinal epithelial barrier, is essential for colonic epithelial homeostasis. However, whether and how Piezo1 regulates colon stem cell fate remains unclear. Here, we show that Piezo1 inhibition promotes colon stem cell proliferation. Mechanistically, stearoyl-CoA 9-desaturase 1 (SCD1) is downstream of Piezo1 to affect colon stem cell stemness by acting on the Wnt-β-catenin pathway. For mice, the altered colon stem cell stemness after Piezo1 knockdown and activation was accompanied by a reprogrammed fatty acid (FA) metabolism in colon crypts. Notably, we found that GsMTX4 protects injured colon stem cell stemness in mouse and human colitis organoids. Our results elucidated the role of Piezo1 in regulating normal and postinjury colon stem cell fates through SCD1-Wnt-β-catenin and the SCD1-mediated FA desaturation process. These results provide fresh perspectives on the mechanical factors regulating colon stem cell fate and therapeutic strategies for related intestinal diseases.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115400"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Random compressed coding with neurons. 神经元随机压缩编码
IF 7.5 1区 生物学
Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-19 DOI: 10.1016/j.celrep.2025.115412
Simone Blanco Malerba, Mirko Pieropan, Yoram Burak, Rava Azeredo da Silveira
{"title":"Random compressed coding with neurons.","authors":"Simone Blanco Malerba, Mirko Pieropan, Yoram Burak, Rava Azeredo da Silveira","doi":"10.1016/j.celrep.2025.115412","DOIUrl":"10.1016/j.celrep.2025.115412","url":null,"abstract":"<p><p>Classical models of efficient coding in neurons assume simple mean responses-\"tuning curves\"- such as bell-shaped or monotonic functions of a stimulus feature. Real neurons, however, can be more complex: grid cells, for example, exhibit periodic responses that impart the neural population code with high accuracy. But do highly accurate codes require fine-tuning of the response properties? We address this question with the use of a simple model: a population of neurons with random, spatially extended, and irregular tuning curves. Irregularity enhances the local resolution of the code but gives rise to catastrophic, global errors. For optimal smoothness of the tuning curves, when local and global errors balance out, the neural population compresses information about a continuous stimulus into a low-dimensional representation, and the resulting distributed code achieves exponential accuracy. An analysis of recordings from monkey motor cortex points to such \"compressed efficient coding.\" Efficient codes do not require a finely tuned design-they emerge robustly from irregularity or randomness.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115412"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lung CD4+ resident memory T cells use airway secretory cells to stimulate and regulate onset of allergic airway neutrophilic disease.
IF 7.5 1区 生物学
Cell reports Pub Date : 2025-03-25 Epub Date: 2025-02-17 DOI: 10.1016/j.celrep.2025.115294
Vijay Raaj Ravi, Filiz T Korkmaz, Carolina Lyon De Ana, Lu Lu, Feng-Zhi Shao, Christine V Odom, Kimberly A Barker, Aditya Ramanujan, Emma N Niszczak, Wesley N Goltry, Ian M C Martin, Catherine T Ha, Lee J Quinton, Matthew R Jones, Alan Fine, Joshua D Welch, Felicia Chen, Anna C Belkina, Joseph P Mizgerd, Anukul T Shenoy
{"title":"Lung CD4<sup>+</sup> resident memory T cells use airway secretory cells to stimulate and regulate onset of allergic airway neutrophilic disease.","authors":"Vijay Raaj Ravi, Filiz T Korkmaz, Carolina Lyon De Ana, Lu Lu, Feng-Zhi Shao, Christine V Odom, Kimberly A Barker, Aditya Ramanujan, Emma N Niszczak, Wesley N Goltry, Ian M C Martin, Catherine T Ha, Lee J Quinton, Matthew R Jones, Alan Fine, Joshua D Welch, Felicia Chen, Anna C Belkina, Joseph P Mizgerd, Anukul T Shenoy","doi":"10.1016/j.celrep.2025.115294","DOIUrl":"10.1016/j.celrep.2025.115294","url":null,"abstract":"<p><p>Neutrophilic asthma is a vexing disease, but mechanistic and therapeutic advancements will require better models of allergy-induced airway neutrophilia. Here, we find that periodic ovalbumin (OVA) inhalation in sensitized mice elicits rapid allergic airway inflammation and pathophysiology mimicking neutrophilic asthma. OVA-experienced murine lungs harbor diverse clusters of CD4<sup>+</sup> resident memory T (T<sub>RM</sub>) cells, including unconventional RORγt<sup>negative/low</sup> T helper 17 (T<sub>H</sub>17) cells. Acute OVA challenge instigates interleukin (IL)-17A secretion from these T<sub>RM</sub> cells, driving CXCL5 production from Muc5ac<sup>high</sup> airway secretory cells, leading to destructive airway neutrophilia. The T<sub>RM</sub> and epithelial cell signals discovered herein are also observed in adult human asthmatic airways. Epithelial antigen presentation regulates this biology by skewing T<sub>RM</sub> cells toward T<sub>H</sub>2 and T<sub>H</sub>1 fates so that T<sub>H</sub>1-related interferon (IFN)-γ suppresses IL-17A-driven, CXCL5-mediated airway neutrophilia. Concordantly, in vivo IFN-γ supplementation improves disease outcomes. Thus, using our model of neutrophilic asthma, we identify lung epithelial-CD4<sup>+</sup> T<sub>RM</sub> cell crosstalk as a key rheostat of allergic airway neutrophilia.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":" ","pages":"115294"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Decoding the structural basis of ligand recognition and biased signaling in the motilin receptor.
IF 7.5 1区 生物学
Cell reports Pub Date : 2025-03-25 Epub Date: 2025-02-22 DOI: 10.1016/j.celrep.2025.115329
Chongzhao You, Mengting Jiang, Tianyu Gao, Zining Zhu, Xinheng He, Youwei Xu, Yuan Gao, Yi Jiang, H Eric Xu
{"title":"Decoding the structural basis of ligand recognition and biased signaling in the motilin receptor.","authors":"Chongzhao You, Mengting Jiang, Tianyu Gao, Zining Zhu, Xinheng He, Youwei Xu, Yuan Gao, Yi Jiang, H Eric Xu","doi":"10.1016/j.celrep.2025.115329","DOIUrl":"10.1016/j.celrep.2025.115329","url":null,"abstract":"<p><p>The motilin receptor (MTLR) is a key target for treating gastrointestinal (GI) disorders like gastroparesis, yet developing effective agonists remains challenging due to drug tolerance and signaling bias. We present cryoelectron microscopy (cryo-EM) structures of MTLR bound to azithromycin, a macrolide antibiotic, and DS-3801b, a non-macrolide agonist. Distinct ligand recognition mechanisms are revealed, with azithromycin binding deeply within the orthosteric pocket and DS-3801b adopting a special clamp-like conformation stabilized by a water molecule. We also highlight the critical role of extracellular loop 2 (ECL2) in ligand specificity and signaling pathway activation, affecting both G-protein and β-arrestin signaling. Additionally, the \"D<sup>2.60</sup>R<sup>2.63</sup>S<sup>3.28</sup>\" motif and interactions around transmembranes 6/7 (TM6/7) are identified as key drivers of signaling selectivity. These findings offer insights into the structural dynamics of MTLR, laying the groundwork for the rational design of next-generation GI prokinetic drugs with enhanced efficacy and safety.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115329"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Area-specific encoding of temporal information in the neocortex.
IF 7.5 1区 生物学
Cell reports Pub Date : 2025-03-25 Epub Date: 2025-02-28 DOI: 10.1016/j.celrep.2025.115363
Anna Christina Garvert, Malte Bieler, Aree Witoelar, Koen Vervaeke
{"title":"Area-specific encoding of temporal information in the neocortex.","authors":"Anna Christina Garvert, Malte Bieler, Aree Witoelar, Koen Vervaeke","doi":"10.1016/j.celrep.2025.115363","DOIUrl":"10.1016/j.celrep.2025.115363","url":null,"abstract":"<p><p>Episodic memory requires remembering the temporal sequence of events, a process attributed to hippocampal \"time cells.\" However, the distributed nature of brain areas supporting episodic memory suggests that temporal representations may extend beyond the hippocampus. To investigate this possibility, we trained mice to remember the identity of an odor for a specific duration. Using mesoscale two-photon imaging of neuronal activity across the neocortex, we reveal a striking area-specific temporal representation. The retrosplenial cortex (RSC), a hippocampal target area, exhibits time-dependent sequential neuronal firing that encodes both odor identity and elapsed time, with decreasing accuracy over time. By contrast, temporal coding is far less prominent in areas surrounding the RSC, including the posterior parietal cortex and visual, somatosensory, and motor areas, highlighting functional specialization. Our results establish the RSC as a key temporal processing hub for episodic memory, supporting conjunctive \"what\" and \"when\" coding models.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115363"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization and host range prediction of Staphylococcus aureus phages through receptor-binding protein analysis.
IF 7.5 1区 生物学
Cell reports Pub Date : 2025-03-25 Epub Date: 2025-02-28 DOI: 10.1016/j.celrep.2025.115369
Janes Krusche, Christian Beck, Esther Lehmann, David Gerlach, Ellen Daiber, Christoph Mayer, Jennifer Müller, Hadil Onallah, Silvia Würstle, Christiane Wolz, Andreas Peschel
{"title":"Characterization and host range prediction of Staphylococcus aureus phages through receptor-binding protein analysis.","authors":"Janes Krusche, Christian Beck, Esther Lehmann, David Gerlach, Ellen Daiber, Christoph Mayer, Jennifer Müller, Hadil Onallah, Silvia Würstle, Christiane Wolz, Andreas Peschel","doi":"10.1016/j.celrep.2025.115369","DOIUrl":"10.1016/j.celrep.2025.115369","url":null,"abstract":"<p><p>Bacteriophages are crucial in bacterial communities and can be used for therapy of multidrug-resistant pathogens such as Staphylococcusaureus. However, the host range of new phages remains difficult to predict. We identified the receptor-binding proteins (RBPs) of 335 S. aureus-infecting phages, yielding 8 distinct RBP clusters. Recombinant representative RBPs of all clusters, including several subclusters, were analyzed for binding to S. aureus strains differing in potential phage receptor structures. Notably, most of the phages encoded two separate RBPs, and all RBPs used S. aureus wall teichoic acid (WTA) polymers as receptors, albeit with varying preference for WTA glycosylation patterns and backbone structures. Based on these findings, a sequence-based tool for predicting the adsorption of new phages was developed. Moreover, one of the RBPs proved useful for identifying S. aureus-type WTA in other bacterial species. These findings facilitate the characterization of phage and bacterial isolates and the development of phage therapies.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115369"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Toward a health-associated core keystone index for the human gut microbiome.
IF 7.5 1区 生物学
Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-01 DOI: 10.1016/j.celrep.2025.115378
Abhishek Goel, Omprakash Shete, Sourav Goswami, Amit Samal, Lavanya C B, Saurabh Kedia, Vineet Ahuja, Paul W O'Toole, Fergus Shanahan, Tarini Shankar Ghosh
{"title":"Toward a health-associated core keystone index for the human gut microbiome.","authors":"Abhishek Goel, Omprakash Shete, Sourav Goswami, Amit Samal, Lavanya C B, Saurabh Kedia, Vineet Ahuja, Paul W O'Toole, Fergus Shanahan, Tarini Shankar Ghosh","doi":"10.1016/j.celrep.2025.115378","DOIUrl":"10.1016/j.celrep.2025.115378","url":null,"abstract":"<p><p>A robust index of gut microbiome taxa encompassing their association with host health and microbiome resilience would be valuable for development and optimization of microbiome-based therapeutics. Here we present a single ranked order for 201 taxa, the Health-Associated Core Keystone (HACK) index, derived using their association strengths with prevalence/community association in non-diseased subjects, longitudinal stability, and host health. The index was derived based on 127 discovery cohorts and 14 validation datasets (cumulatively encompassing 45,424 gut microbiomes, subject age >18 years, representing 42 countries, 28 disease categories, and 10,021 longitudinal samples). We show that this index is reproducible regardless of microbiome profiling strategies and cohort lifestyle. Specific consortia of high HACK index taxa respond positively to Mediterranean diet interventions and reflect immune checkpoint inhibitor responsiveness and associated with specific functional profiles at the genome level. The availability of HACK indices provides a rational basis for comparing microbiomes and facilitating selection and design of microbiome-based therapeutics.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115378"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tissue-resident CCR2+ macrophage TREM-1/3 signaling is necessary for monocyte and neutrophil recruitment to injured hearts.
IF 7.5 1区 生物学
Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-04 DOI: 10.1016/j.celrep.2025.115380
Yuriko Terada, Wenjun Li, Junedh M Amrute, Amit I Bery, Charles R Liu, Venkatrao Nunna, Christian Corbin Frye, Hao Dun, Andrew L Koenig, Hannah P Luehmann, Gyu Seong Heo, Macee C Owen, Alexander N Wein, Yongjian Liu, Jon H Ritter, Sumanth D Prabhu, Ruben G Nava, Andrew E Gelman, Marina Cella, Marco Colonna, Kory J Lavine, Daniel Kreisel
{"title":"Tissue-resident CCR2<sup>+</sup> macrophage TREM-1/3 signaling is necessary for monocyte and neutrophil recruitment to injured hearts.","authors":"Yuriko Terada, Wenjun Li, Junedh M Amrute, Amit I Bery, Charles R Liu, Venkatrao Nunna, Christian Corbin Frye, Hao Dun, Andrew L Koenig, Hannah P Luehmann, Gyu Seong Heo, Macee C Owen, Alexander N Wein, Yongjian Liu, Jon H Ritter, Sumanth D Prabhu, Ruben G Nava, Andrew E Gelman, Marina Cella, Marco Colonna, Kory J Lavine, Daniel Kreisel","doi":"10.1016/j.celrep.2025.115380","DOIUrl":"10.1016/j.celrep.2025.115380","url":null,"abstract":"<p><p>Triggering receptor expressed on myeloid cells 1 (TREM-1) has been shown to amplify inflammatory signals, such as Toll-like receptor signaling, after infection and sterile injury. While previous studies have demonstrated that TREM-1 activation in circulating immune cells promotes injury, the role of TREM-1 signaling in tissue-resident cells in the context of sterile inflammation remains poorly understood. Here, we used a cardiac transplantation model to dissect how Trem1/3 expression on heart-resident cells regulates sterile inflammation. TREM-1 is expressed in heart-resident C-C chemokine receptor 2 (CCR2)<sup>+</sup> macrophages in mice and humans. TREM-1/3 signaling in tissue-resident CCR2<sup>+</sup> macrophages promotes C-C motif chemokine ligand 3 (CCL3) production and is critical for recruiting neutrophils and CCR2<sup>+</sup> monocytes after heart transplantation. We demonstrate prolonged allograft survival after transplantation of Trem1/3-deficient compared with wild-type hearts. We identify TREM-1/3 signaling in donor grafts as a potential future therapeutic target to blunt inflammation after myocardial ischemia-reperfusion injury.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115380"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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