首页|Integrated NLRP3,AIM2,NLRC4,Pyrin inflammasome activation and assembly drive PANoptosis
Integrated NLRP3,AIM2,NLRC4,Pyrin inflammasome activation and assembly drive PANoptosis
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
万方数据
Inflammasomes are important sentinels of innate immune defense;they sense pathogens and induce the cell death of infected cells,playing key roles in inflammation,development,and cancer.Several inflammasome sensors detect and respond to specific pathogen-and damage-associated molecular patterns(PAMPs and DAMPs,respectively)by forming a multiprotein complex with the adapters ASC and caspase-1.During disease,cells are exposed to several PAMPs and DAMPs,leading to the concerted activation of multiple inflammasomes.However,the molecular mechanisms that integrate multiple inflammasome sensors to facilitate optimal host defense remain unknown.Here,we discovered that simultaneous inflammasome activation by multiple ligands triggered multiple types of programmed inflammatory cell death,and these effects could not be mimicked by treatment with a pure ligand of any single inflammasome.Furthermore,NLRP3,AIM2,NLRC4,and Pyrin were determined to be members of a large multiprotein complex,along with ASC,caspase-1,caspase-8,and RIPK3,and this complex drove PANoptosis.Furthermore,this multiprotein complex was released into the extracellular space and retained as multiple inflammasomes.Multiple extracellular inflammasome particles could induce inflammation after their engulfment by neighboring macrophages.Collectively,our findings define a previously unknown regulatory connection and molecular interaction between inflammasome sensors,which drives the assembly of a multiprotein complex that includes multiple inflammasome sensors and cell death regulators.The discovery of critical interactions among NLRP3,AIM2,NLRC4,and Pyrin represents a new paradigm in understanding the functions of these molecules in innate immunity and inflammasome biology as well as identifying new therapeutic targets for NLRP3-,AIM2-,NLRC4-and Pyrin-mediated diseases.
SuHyeon Oh、Jihye Lee、Jueun Oh、Gyoengju Yu、Haesun Ryu、Daesik Kim、SangJoon Lee
展开 >
Department of Biological Science,Ulsan National Institute of Science and Technology(UNIST),Ulsan,Republic of Korea
Department of Precision Medicine,Sungkyunkwan University School of Medicine,Suwon,Republic of Korea
National Research Foundation of Korea(NRF)grant that was funded by the Korean government(MSIT)Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)Ministry of Health &Welfare,Republic of KoreaNational Institute of Health,Republic of KoreaInstitute for Basic Science(IBS)Republic of Koreaa research fund from Ulsan National Institute of Science & Technology(UNIST)a research fund from Ulsan National Institute of Science & Technology(UNIST)Yuhan Corporation(SL)National Research Foundation of Korea(NRF)Center for Women In Science,Engineering and Technology(WISET)Ministry of Science and ICT(MSIT)under the Program for Returners into R&D
万方数据
