Review
Immunology
Ruixuan You, Xinglan He, Zhuotong Zeng, Yi Zhan, Yangfan Xiao, Rong Xiao
Summary: Autoimmune diseases are a group of heterogeneous diseases caused by the destruction of immune tolerance and the production of autoantibodies. Excessive exacerbation of pyroptosis, a form of programmed cell death, plays a crucial role in the development of autoimmune diseases. Inflammasomes act as switches for pyroptosis, and various pyroptosis pathways disrupt immune system homeostasis and promote autoimmunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Lee M. Booty, Clare E. Bryant
Summary: The discovery of pyroptosis and its implications in infection and immunity has provided new insights into host defense against pathogens. However, the regulation of pyroptosis is complex and varies between cell types, stimulation conditions, pathogens, and animal species. Excessive inflammation caused by pyroptosis contributes to the development of sepsis. Understanding the regulation of pyroptotic pathways is crucial for identifying potential therapeutic targets for sepsis.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Medicine, Research & Experimental
Zuohao Liu, Chunming Wang, Changjun Lin
Summary: Pyroptosis is a recently discovered programmed cell death mode caused by inflammasomes and Gasdermin family proteins. It leads to the release of inflammatory factors and triggers an inflammatory cascade response. Pyroptosis has different morphological features compared to other cell death modes and can be a potential cancer treatment strategy. However, there is still much unknown about its molecular mechanisms in pathogenicity and therapeutics, requiring further research.
Article
Immunology
Yiting Tang, Xiangyu Wang, Zhaozheng Li, Zhihui He, Xinyu Yang, Xiaoye Cheng, Yue Peng, Qianqian Xue, Yang Bai, Rui Zhang, Kai Zhao, Fang Liang, Xianzhong Xiao, Ulf Andersson, Haichao Wang, Timothy R. Billiar, Ben Lu
Summary: Heparin prevents immune responses and reduces mortality in sepsis independently of its anticoagulant properties. This previously unrecognized function of heparin reveals a link between innate immune responses and coagulation.
Review
Immunology
Claudine S. S. Greenwood, Meghan A. A. Wynosky-Dolfi, Allison M. M. Beal, Lee M. M. Booty
Summary: The discovery of gasdermin D (GSDMD) as the terminal executioner of pyroptosis fills an important gap in our understanding of cell death and highlights the significance of the gasdermin family. GSDMD connects the innate alarm systems to an explosive, inflammatory form of cell death, triggering immunological responses in the local environment.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ruo-Nan Zhang, Zhi-Jun Sun, Lu Zhang
Summary: Inflammatory bone diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA), cause severe bone damage and bring significant medical costs to patients' families and government agencies. The complexity of osteoimmunology has made it challenging to research these diseases. Understanding the potential mechanisms and finding effective drugs to target inflammatory bone diseases is urgent. Pyroptosis, a necrotic cell death featuring the secretion of pro-inflammatory cytokines, has been identified as a vital component in the etiopathogenesis of these diseases. This review discusses the characteristics and mechanisms of pyroptosis and its clinical significance in inflammatory bone diseases. The current research progress of drugs targeting pyroptosis for enhancing therapeutic efficacy is also summarized, providing new insights for future directions.
Article
Gastroenterology & Hepatology
Yi-Long Wu, Wei-Jie Ou, Ming Zhong, Su Lin, Yue-Yong Zhu
Summary: This study found that the GSDMD inhibitor NSA can alleviate ALF by reducing the activation of pyroptosis, providing a new perspective for the treatment of ALF.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Yi-Long Wu, Wei-Jie Ou, Ming Zhong, Su Lin, Yue-Yong Zhu
Summary: This study discovered that pyroptosis is activated in acute liver failure (ALF) models, and the use of GSDMD inhibitor NSA can alleviate ALF.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Julia Nowowiejska, Anna Baran, Justyna Magdalena Hermanowicz, Anna Pryczynicz, Beata Sieklucka, Dariusz Pawlak, Iwona Flisiak
Summary: Psoriasis is an important issue in dermatological practice, causing both aesthetic and quality of life concerns. The pathogenesis of psoriasis remains uncertain, but GSDMD, a protein involved in cell inflammation, proliferation, and death, may play a role. The study found increased expression of GSDMD in psoriatic skin, but no significant differences in serum and urinary GSDMD concentrations between psoriasis patients and controls.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Zixi Song, Jiahong Zou, Mengya Wang, Zhenwei Chen, Qingchao Wang
Summary: Pyroptosis is a programmed cell death process executed by gasdermin family proteins. In fish, it mainly depends on NLRP3 inflammasome and is influenced by pathogenic microorganism infection and environmental pollutants.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Pauline Puylaert, Melissa Van Praet, Frederik Vaes, Cedric H. G. Neutel, Lynn Roth, Pieter-Jan Guns, Guido R. Y. De Meyer, Wim Martinet
Summary: GSDMD plays a critical role in atherosclerotic plaque destabilization, with its deficiency leading to increased plaque stability and apoptosis. Targeting GSDMD may be an effective approach to limit the transition to an inflammatory, vulnerable plaque phenotype.
Review
Oncology
Xiuxia Lu, Tianhui Guo, Xing Zhang
Summary: Pyroptosis, a new form of programmed cell death, has garnered attention in cancer research. Various stimuli can trigger pyroptosis, but its role in cancer remains unclear with conflicting findings. Despite the uncertainties, pyroptosis may hold potential as a promising anti-cancer therapy.
Review
Biochemistry & Molecular Biology
Qiuyun Jiang, Zhigang Zhu, Xinliang Mao
Summary: Inflammasomes serve as a vital component in the innate immune system to defend against disruptions in homeostasis caused by pathogens or host molecules. Comprised of protein complexes, these inflammasomes assemble in the cytosol upon detection of danger signals. Activation of inflammasomes leads to the release of pro-inflammatory cytokines and pyroptotic cell death. Recent studies have highlighted the role of protein post-translational modifications, particularly ubiquitination, in modulating inflammasome activation. Understanding these mechanisms could offer new strategies for targeting diseases associated with the inflammasome pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
Article
Biochemistry & Molecular Biology
Dhruv Chauhan, Dieter Demon, Lieselotte Vande Walle, Oonagh Paerewijck, Annalisa Zecchin, Leslie Bosseler, Karin Santoni, Remi Planes, Silvia Ribo, Amelie Fossoul, Amanda Goncalves, Hanne Van Gorp, Nina Van Opdenbosch, Filip Van Hauwermeiren, Etienne Meunier, Andy Wullaert, Mohamed Lamkanfi
Summary: This study confirms the presence of multiple canonical inflammasomes in neutrophils and identifies their differential roles in neutrophil immune responses. It provides new insights into the immune mechanisms of neutrophils.
Article
Pharmacology & Pharmacy
Lin Gao, Xiaowu Dong, Weijuan Gong, Wei Huang, Jing Xue, Qingtian Zhu, Nan Ma, Weiwei Chen, Xianghui Fu, Xiang Gao, Zhaoyu Lin, Yanbing Ding, Juanjuan Shi, Zhihui Tong, Tingting Liu, Rajarshi Mukherjee, Robert Sutton, Guotao Lu, Weiqin Li
Summary: This study reveals the critical role of NLRP3 inflammasome and GSDMD activation-mediated pyroptosis in acinar cells, linking pancreatic necrosis and systemic inflammation in acute pancreatitis. Targeting pyroptosis signaling pathways holds promise for specific therapy for acute pancreatitis.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Joseph K. Rathkey, Tsan S. Xiao, Derek W. Abbott
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Sukanya Srinivasan, Zhonghua Liu, Watchalee Chuenchor, Tsan Sam Xiao, Eckhard Jankowsky
JOURNAL OF MOLECULAR BIOLOGY
(2020)
Article
Biochemical Research Methods
Xing-Huang Gao, Ling Li, Marc Parisien, Jing Wu, Ilya Bederman, Zhaofeng Gao, Dawid Krokowski, Steven M. Chirieleison, Derek Abbott, Benlian Wang, Peter Arvan, Mark Cameron, Mark Chance, Belinda Willard, Maria Hatzoglou
MOLECULAR & CELLULAR PROTEOMICS
(2020)
Article
Multidisciplinary Sciences
Huacheng Luo, Qin Yu, Yang Liu, Ming Tang, Mingwei Liang, Dingpeng Zhang, Tsan Sam Xiao, Lizi Wu, Ming Tan, Yijun Ruan, Jorg Bungert, Jianrong Lu
Article
Immunology
Chun Zhou, Xia Chen, Rosa Planells-Cases, Jiachen Chu, Li Wang, Limin Cao, Zhihong Li, Karen Lopez-Cayuqueo, Yadong Xie, Shiwei Ye, Xiang Wang, Florian Ullrich, Shixin Ma, Yiyuan Fang, Xiaoming Zhang, Zhikang Qian, Xiaozheng Liang, Shi-Qing Cai, Zhengfan Jiang, Dongming Zhou, Qibin Leng, Tsan S. Xiao, Ke Lan, Jinbo Yang, Huabin Li, Chao Peng, Zhaozhu Qiu, Thomas J. Jentsch, Hui Xiao
Review
Biochemistry & Molecular Biology
Christopher B. Ryder, Hannah C. Kondolf, Meghan E. O'Keefe, Bowen Zhou, Derek W. Abbott
Summary: This review discusses the biological functions of Gasdermin proteins in pyroptosis and their potential as therapeutic targets for human diseases.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jie Yang, Albert S. Song, R. Luke C. Wiseman, Gabriel Lander
Summary: Lon protease in yeast, known as PIM1, has unique structural and functional features. Our study revealed the hexameric structure of PIM1 and the role of ATPase domains in substrate translocation. We also found a unique C-terminal extension in the protease domain. The yeast-specific insertion was shown to be dispensable for PIM1's enzymatic function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Shrikanth C. Basavarajappa, Angela Rose Liu, Anna Bruchez, Zhenlu Li, Vinicius G. Suzart, Zhonghua Liu, Yinghua Chen, Tsan Sam Xiao, Matthias Buck, Parameswaran Ramakrishnan
Summary: The modified trimeric RBD shows higher affinity binding to ACE2 and more effectively blocks CoV-2 infection compared to the monomeric RBD, indicating its potential as a first-line therapeutic method to control COVID-19.
Article
Immunology
Cheryl C. Collins, Peter Hahn, Zhaozhao Jiang, Katherine A. Fitzgerald, Tsan Sam Xiao, Ralph C. Budd
Summary: gd T cells are found at mucosal and epithelial barriers and tend to accumulate at sites of inflammation, infection, autoimmunity, and certain tumors. The ligands recognized by the gd T cell receptor (TCR) and the regulation of their expression are not fully understood. In this study, a soluble human TCR-gd tetramer was developed and shown to bind to monocytes activated by Borrelia burgdorferi, the causative agent of Lyme arthritis. Ligand expression on monocytes was found to be induced by Toll-like receptor agonists and dependent on NF-kB activation, caspase activation of the inflammasome, active metabolism, mitochondrial reactive oxygen species, and gasdermin-D activation. The ligand was expressed by a subset of metabolically active CD14+CD16+ monocytes and colocalized with mitochondria. These findings suggest that the synovial gd T cell ligand is a self-antigen whose expression is increased under inflammatory conditions and mitochondrial stress.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Yuan Tian, Ishara Datta, Rui Yang, Chun Wan, Bing Wang, Lauren Crisman, Huan He, Chad A. Brautigam, Suzhao Li, Jingshi Shen, Qian Yin
Summary: We found that AAGAB exists as a dimer before binding to AP1/2, and its dimerization is mediated by the C-terminal domain. AAGAB uses the same C-terminal domain to recognize and stabilize the subunits in the AP1 and AP2 complexes, forming binary complexes with only one copy of AAGAB.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Bowen Zhou, Christopher B. Ryder, George R. Dubyak, Derek W. Abbott
Summary: This study reveals that pyroptotic cell death is an integrated network mechanism mediated by the gasdermin family. Caspase-1 and caspase-3 play different roles in activating gasdermins under inflammatory and apoptotic conditions, respectively. The study also identifies PANX1 as a crucial channel protein involved in chemotherapy-induced pyroptosis.
Article
Biochemistry & Molecular Biology
Yamu Li, Zhonghua Liu, Yiqing Zhao, Jie Yang, Tsan Sam Xiao, Ronald A. Conlon, Zhenghe Wang
Summary: This study reveals that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers. ERBB3 modulates IFN-g-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling axis. Additionally, ERBB3 mutations could serve as predictive biomarkers for tumors amenable to immune checkpoint therapy.
Article
Biochemistry & Molecular Biology
Jie Yang, Kelsey R. Baron, Daniel E. Pride, Anette Schneemann, Xiaoyan Guo, Wenqian Chen, Albert S. Song, Giovanni Aviles, Martin Kampmann, R. Luke Wiseman, Gabriel C. Lander
Summary: In this study, researchers discovered that the cleavage product of DELE1 induced by mitochondrial stress forms a signaling platform that triggers the integrated stress response. They determined the cryo-electron microscopy structure of the C-terminal cleavage product of human DELE1, which assembles into a high-order oligomer. The assembly-impaired DELE1 mutants were found to have compromised activation of HRI-dependent integrated stress response.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Immunology
Bowen Zhou, Derek W. Abbott
Summary: This article discusses the current research progress on three inhibitors affecting the activity of gasdermin D and provides cautionary notes, as well as a set of guiding principles for researchers to consider when further studying gasdermin D inhibition.
SEMINARS IN IMMUNOLOGY
(2023)