Mengtian Shan, Song Zhang, Zhibing Luo, Shengjie Deng, Linyu Ran, Quan Zhou, Huimin Wan, Jihui Ye, Chenchen Qian, Ximin Fan, Yun Feng, David W. Morse, Joerg Herrmann, Qiang Li, Zhongliang Guo, Feilong Wang
{"title":"衣康酸促进组织内肺泡巨噬细胞的炎症反应,加重急性肺损伤","authors":"Mengtian Shan, Song Zhang, Zhibing Luo, Shengjie Deng, Linyu Ran, Quan Zhou, Huimin Wan, Jihui Ye, Chenchen Qian, Ximin Fan, Yun Feng, David W. Morse, Joerg Herrmann, Qiang Li, Zhongliang Guo, Feilong Wang","doi":"10.1016/j.cmet.2025.05.012","DOIUrl":null,"url":null,"abstract":"Itaconate is an anti-inflammatory metabolite with therapeutic potential in multiple inflammatory diseases. However, its immunomodulatory function has been mainly based on <em>ex vivo</em>-generated macrophages or cell lines, whereas its role in tissue-resident macrophages is still poorly understood. Here, we report that, in contrast to its effects on bone-marrow-derived macrophages (BMDMs), itaconate promotes the production of proinflammatory cytokines and augments the activation of the NACHT-, leucine-rich-repeat- (LRR), and pyrin domain-containing protein 3 (NLRP3) inflammasome in resident alveolar macrophages (AMs). Unlike native itaconate, the itaconate derivatives dimethyl itaconate (DI) and 4-octyl itaconate (4OI) suppress the inflammatory response in AMs. Notably, the intratracheal transfer of BMDMs reversed their responsiveness to itaconate, indicating an essential role of the alveolar microenvironment in shaping macrophage immunometabolism. We also demonstrate that itaconate promotes AM-mediated inflammatory responses <em>in vivo</em> and aggravates lung injury. Taken together, our study unexpectedly demonstrates a proinflammatory role of itaconate in tissue-resident AMs, suggesting that further investigations are needed before its clinical application.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"10 1","pages":""},"PeriodicalIF":27.7000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Itaconate promotes inflammatory responses in tissue-resident alveolar macrophages and exacerbates acute lung injury\",\"authors\":\"Mengtian Shan, Song Zhang, Zhibing Luo, Shengjie Deng, Linyu Ran, Quan Zhou, Huimin Wan, Jihui Ye, Chenchen Qian, Ximin Fan, Yun Feng, David W. Morse, Joerg Herrmann, Qiang Li, Zhongliang Guo, Feilong Wang\",\"doi\":\"10.1016/j.cmet.2025.05.012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Itaconate is an anti-inflammatory metabolite with therapeutic potential in multiple inflammatory diseases. However, its immunomodulatory function has been mainly based on <em>ex vivo</em>-generated macrophages or cell lines, whereas its role in tissue-resident macrophages is still poorly understood. Here, we report that, in contrast to its effects on bone-marrow-derived macrophages (BMDMs), itaconate promotes the production of proinflammatory cytokines and augments the activation of the NACHT-, leucine-rich-repeat- (LRR), and pyrin domain-containing protein 3 (NLRP3) inflammasome in resident alveolar macrophages (AMs). Unlike native itaconate, the itaconate derivatives dimethyl itaconate (DI) and 4-octyl itaconate (4OI) suppress the inflammatory response in AMs. Notably, the intratracheal transfer of BMDMs reversed their responsiveness to itaconate, indicating an essential role of the alveolar microenvironment in shaping macrophage immunometabolism. We also demonstrate that itaconate promotes AM-mediated inflammatory responses <em>in vivo</em> and aggravates lung injury. Taken together, our study unexpectedly demonstrates a proinflammatory role of itaconate in tissue-resident AMs, suggesting that further investigations are needed before its clinical application.\",\"PeriodicalId\":9840,\"journal\":{\"name\":\"Cell metabolism\",\"volume\":\"10 1\",\"pages\":\"\"},\"PeriodicalIF\":27.7000,\"publicationDate\":\"2025-06-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell metabolism\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cmet.2025.05.012\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell metabolism","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cmet.2025.05.012","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Itaconate promotes inflammatory responses in tissue-resident alveolar macrophages and exacerbates acute lung injury
Itaconate is an anti-inflammatory metabolite with therapeutic potential in multiple inflammatory diseases. However, its immunomodulatory function has been mainly based on ex vivo-generated macrophages or cell lines, whereas its role in tissue-resident macrophages is still poorly understood. Here, we report that, in contrast to its effects on bone-marrow-derived macrophages (BMDMs), itaconate promotes the production of proinflammatory cytokines and augments the activation of the NACHT-, leucine-rich-repeat- (LRR), and pyrin domain-containing protein 3 (NLRP3) inflammasome in resident alveolar macrophages (AMs). Unlike native itaconate, the itaconate derivatives dimethyl itaconate (DI) and 4-octyl itaconate (4OI) suppress the inflammatory response in AMs. Notably, the intratracheal transfer of BMDMs reversed their responsiveness to itaconate, indicating an essential role of the alveolar microenvironment in shaping macrophage immunometabolism. We also demonstrate that itaconate promotes AM-mediated inflammatory responses in vivo and aggravates lung injury. Taken together, our study unexpectedly demonstrates a proinflammatory role of itaconate in tissue-resident AMs, suggesting that further investigations are needed before its clinical application.
期刊介绍:
Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others.
Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.