INVITED REVIEW
PANoptosis: Mechanisms, biology, and role in disease
Xu Sun,
Yanpeng Yang,
Xiaona Meng,
Jia Li,
Xiaoli Liu,
Huaimin Liu,
Xu Sun
Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
Search for more papers by this authorYanpeng Yang
Cardiac Care Unit, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
Search for more papers by this authorXiaona Meng
Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
Search for more papers by this authorJia Li
Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
Search for more papers by this authorXiaoli Liu
Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
Search for more papers by this authorCorresponding Author
Huaimin Liu
Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
Correspondence
Huaimin Liu, Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450008, Henan, China.
Email: [email protected]
Search for more papers by this authorXu Sun,
Yanpeng Yang,
Xiaona Meng,
Jia Li,
Xiaoli Liu,
Huaimin Liu,
Xu Sun
Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
Search for more papers by this authorYanpeng Yang
Cardiac Care Unit, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
Search for more papers by this authorXiaona Meng
Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
Search for more papers by this authorJia Li
Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
Search for more papers by this authorXiaoli Liu
Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
Search for more papers by this authorCorresponding Author
Huaimin Liu
Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
Correspondence
Huaimin Liu, Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450008, Henan, China.
Email: [email protected]
Search for more papers by this authorThis article is part of a series of reviews covering Mechanisms of programmed cell death appearing in Volume 321 of Immunological Reviews.
Summary
Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell death modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which can be mediated by multifaceted PANoptosome complexes assembled via integrating components from other cell death modalities. There is growing interest in the process and function of PANoptosis. Accumulating evidence suggests that PANoptosis occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, and cancer. Given the impact of PANoptosis across the disease spectrum, this review briefly describes the relationships between pyroptosis, apoptosis, and necroptosis, highlights the key molecules in PANoptosome formation and PANoptosis activation, and outlines the multifaceted roles of PANoptosis in diseases together with a potential for therapeutic targeting. We also discuss important concepts and pressing issues for future PANoptosis research. Improved understanding of PANoptosis and its mechanisms is crucial for identifying novel therapeutic targets and strategies.
CONFLICT OF INTEREST STATEMENT
The authors declare that there are no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- 1Karki R, Sharma BR, Tuladhar S, et al. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell. 2021; 184(1): 149-168.e117.
- 2Pan H, Pan J, Li P, Gao J. Characterization of PANoptosis patterns predicts survival and immunotherapy response in gastric cancer. Clin Immunol. 2022; 238:109019.
- 3Zheng M, Kanneganti TD. The regulation of the ZBP1-NLRP3 inflammasome and its implications in pyroptosis, apoptosis, and necroptosis (PANoptosis). Immunol Rev. 2020; 297(1): 26-38.
- 4Niu X, Chen L, Li Y, Hu Z, He F. Ferroptosis, necroptosis, and pyroptosis in the tumor microenvironment: perspectives for immunotherapy of SCLC. Semin Cancer Biol. 2022; 86(Pt 3): 273-285.
- 5Fritsch M, Günther SD, Schwarzer R, et al. Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis. Nature. 2019; 575(7784): 683-687.
- 6Bertheloot D, Latz E, Franklin BS. Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol. 2021; 18(5): 1106-1121.
- 7Sundaram B, Pandian N, Mall R, et al. NLRP12-PANoptosome activates PANoptosis and pathology in response to heme and PAMPs. Cell. 2023; 186(13): 2783-2801.e2720.
- 8Yan WT, Zhao WJ, Hu XM, et al. PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons. Neural Regen Res. 2023; 18(2): 357-363.
- 9Chen W, Gullett JM, Tweedell RE, Kanneganti TD. Innate immune inflammatory cell death: PANoptosis and PANoptosomes in host defense and disease. Eur J Immunol. 2023;e2250235.
- 10Lin JF, Hu PS, Wang YY, et al. Phosphorylated NFS1 weakens oxaliplatin-based chemosensitivity of colorectal cancer by preventing PANoptosis. Signal Transduct Target Ther. 2022; 7(1): 54.
- 11Banoth B, Tuladhar S, Karki R, et al. ZBP1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis). J Biol Chem. 2020; 295(52): 18276-18283.
- 12Yoneyama M, Kikuchi M, Natsukawa T, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol. 2004; 5(7): 730-737.
- 13Choi H, Kwon J, Cho MS, et al. Targeting DDX3X triggers antitumor immunity via a dsRNA-mediated tumor-intrinsic type I interferon response. Cancer Res. 2021; 81(13): 3607-3620.
- 14Jiao H, Wachsmuth L, Kumari S, et al. Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation. Nature. 2020; 580(7803): 391-395.
- 15Ahmad S, Mu X, Yang F, et al. Breaching self-tolerance to Alu duplex RNA underlies MDA5-mediated inflammation. Cell. 2018; 172(4): 797-810.e713.
- 16Li S, Fan G, Li X, Cai Y, Liu R. Modulation of type I interferon signaling by natural products in the treatment of immune-related diseases. Chin J Nat Med. 2023; 21(1): 3-18.
- 17Li Y, Guo X, Hu C, et al. Type I IFN operates pyroptosis and necroptosis during multidrug-resistant a. baumannii infection. Cell Death Differ. 2018; 25(7): 1304-1318.
- 18Schwartz T, Behlke J, Lowenhaupt K, Heinemann U, Rich A. Structure of the DLM-1-Z-DNA complex reveals a conserved family of Z-DNA-binding proteins. Nat Struct Biol. 2001; 8(9): 761-765.
- 19Wang R, Li H, Wu J, et al. Gut stem cell necroptosis by genome instability triggers bowel inflammation. Nature. 2020; 580(7803): 386-390.
- 20Kuriakose T, Man SM, Malireddi RK, et al. ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Sci Immunol. 2016; 1(2):aag2045.
- 21Devos M, Tanghe G, Gilbert B, et al. Sensing of endogenous nucleic acids by ZBP1 induces keratinocyte necroptosis and skin inflammation. J Exp Med. 2020; 217(7):e20191913.
- 22Karki R, Kanneganti TD. Diverging inflammasome signals in tumorigenesis and potential targeting. Nat Rev Cancer. 2019; 19(4): 197-214.
- 23Man SM, Kanneganti TD. Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat Rev Immunol. 2016; 16(1): 7-21.
- 24Hughes MM, O'Neill LAJ. Metabolic regulation of NLRP3. Immunol Rev. 2018; 281(1): 88-98.
- 25Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015; 526(7575): 660-665.
- 26Kayagaki N, Stowe IB, Lee BL, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015; 526(7575): 666-671.
- 27Zhang Z, Venditti R, Ran L, et al. Distinct changes in endosomal composition promote NLRP3 inflammasome activation. Nat Immunol. 2023; 24(1): 30-41.
- 28Hsu CG, Li W, Sowden M, Chávez CL, Berk BC. Pnpt1 mediates NLRP3 inflammasome activation by MAVS and metabolic reprogramming in macrophages. Cell Mol Immunol. 2023; 20(2): 131-142.
- 29Higashikuni Y, Liu W, Numata G, et al. NLRP3 Inflammasome activation through heart-brain interaction initiates cardiac inflammation and hypertrophy during pressure overload. Circulation. 2023; 147(4): 338-355.
- 30Zheng M, Karki R, Vogel P, Kanneganti TD. Caspase-6 is a key regulator of innate immunity, Inflammasome activation, and host defense. Cell. 2020; 181(3): 674-687.e613.
- 31Nishikura K. Functions and regulation of RNA editing by ADAR deaminases. Annu Rev Biochem. 2010; 79: 321-349.
- 32Wang Q, Khillan J, Gadue P, Nishikura K. Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis. Science. 2000; 290(5497): 1765-1768.
- 33Liddicoat BJ, Piskol R, Chalk AM, et al. RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science. 2015; 349(6252): 1115-1120.
- 34Hartner JC, Schmittwolf C, Kispert A, Müller AM, Higuchi M, Seeburg PH. Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1. J Biol Chem. 2004; 279(6): 4894-4902.
- 35Tang ZL, Wang S, Tu C, et al. Eight novel mutations of the ADAR1 gene in Chinese patients with Dyschromatosis Symmetrica Hereditaria. Genet Test Mol Biomarkers. 2018; 22(2): 104-108.
- 36Zhang T, Yin C, Fedorov A, et al. ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis. Nature. 2022; 606(7914): 594-602.
- 37Shiromoto Y, Sakurai M, Minakuchi M, Ariyoshi K, Nishikura K. ADAR1 RNA editing enzyme regulates R-loop formation and genome stability at telomeres in cancer cells. Nat Commun. 2021; 12(1): 1654.
- 38Eckmann CR, Neunteufl A, Pfaffstetter L, Jantsch MF. The human but not the Xenopus RNA-editing enzyme ADAR1 has an atypical nuclear localization signal and displays the characteristics of a shuttling protein. Mol Biol Cell. 2001; 12(7): 1911-1924.
- 39Sun T, Yu Y, Wu X, et al. Decoupling expression and editing preferences of ADAR1 p150 and p110 isoforms. Proc Natl Acad Sci U S A. 2021; 118(12):e2021757118.
- 40Schwartz T, Rould MA, Lowenhaupt K, Herbert A, Rich A. Crystal structure of the Zalpha domain of the human editing enzyme ADAR1 bound to left-handed Z-DNA. Science. 1999; 284(5421): 1841-1845.
- 41Karki R, Sundaram B, Sharma BR, et al. ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. Cell Rep. 2021; 37(3):109858.
- 42Kanneganti TD. Intracellular innate immune receptors: life inside the cell. Immunol Rev. 2020; 297(1): 5-12.
- 43Inohara N, Nuñez G. NODs: intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol. 2003; 3(5): 371-382.
- 44Harton JA, Linhoff MW, Zhang J, Ting JP. Cutting edge: CATERPILLER: a large family of mammalian genes containing CARD, pyrin, nucleotide-binding, and leucine-rich repeat domains. J Immunol. 2002; 169(8): 4088-4093.
- 45Lee S, Karki R, Wang Y, Nguyen LN, Kalathur RC, Kanneganti TD. AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence. Nature. 2021; 597(7876): 415-419.
- 46Malireddi RKS, Gurung P, Kesavardhana S, et al. Innate immune priming in the absence of TAK1 drives RIPK1 kinase activity-independent pyroptosis, apoptosis, necroptosis, and inflammatory disease. J Exp Med. 2020; 217(3):jem.20191644.
- 47Malireddi RKS, Gurung P, Mavuluri J, et al. TAK1 restricts spontaneous NLRP3 activation and cell death to control myeloid proliferation. J Exp Med. 2018; 215(4): 1023-1034.
- 48Rajput A, Kovalenko A, Bogdanov K, et al. RIG-I RNA helicase activation of IRF3 transcription factor is negatively regulated by caspase-8-mediated cleavage of the RIP1 protein. Immunity. 2011; 34(3): 340-351.
- 49Ning X, Wang Y, Jing M, et al. Apoptotic caspases suppress type I interferon production via the cleavage of cGAS, MAVS, and IRF3. Mol Cell. 2019; 74(1): 19-31.e17.
- 50White MJ, McArthur K, Metcalf D, et al. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell. 2014; 159(7): 1549-1562.
- 51Rongvaux A, Jackson R, Harman CC, et al. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell. 2014; 159(7): 1563-1577.
- 52Wang Y, Karki R, Mall R, et al. Molecular mechanism of RIPK1 and caspase-8 in homeostatic type I interferon production and regulation. Cell Rep. 2022; 41(1):111434.
- 53Taabazuing CY, Griswold AR, Bachovchin DA. The NLRP1 and CARD8 inflammasomes. Immunol Rev. 2020; 297(1): 13-25.
- 54Malireddi RKS, Bynigeri RR, Mall R, et al. Whole-genome CRISPR screen identifies RAVER1 as a key regulator of RIPK1-mediated inflammatory cell death. PANoptosis iScience. 2023; 26(6):106938.
- 55Henkel FDR, O'Neill LAJ. NLRP12 drives PANoptosis in response to heme. Trends Immunol. 2023; 44(8): 574-576.
- 56Xiong L, Wang S, Dean JW, et al. Group 3 innate lymphoid cell pyroptosis represents a host defence mechanism against salmonella infection. Nat Microbiol. 2022; 7(7): 1087-1099.
- 57Wotzka SY, Nguyen BD, Hardt WD. Salmonella Typhimurium diarrhea reveals basic principles of Enteropathogen infection and disease-promoted DNA exchange. Cell Host Microbe. 2017; 21(4): 443-454.
- 58McClelland M, Sanderson KE, Spieth J, et al. Complete genome sequence of salmonella enterica serovar Typhimurium LT2. Nature. 2001; 413(6858): 852-856.
- 59Keestra-Gounder AM, Tsolis RM, Bäumler AJ. Now you see me, now you don't: the interaction of salmonella with innate immune receptors. Nat Rev Microbiol. 2015; 13(4): 206-216.
- 60Hausmann A, Böck D, Geiser P, et al. Intestinal epithelial NAIP/NLRC4 restricts systemic dissemination of the adapted pathogen salmonella Typhimurium due to site-specific bacterial PAMP expression. Mucosal Immunol. 2020; 13(3): 530-544.
- 61Raffatellu M, Wilson RP, Chessa D, et al. SipA, SopA, SopB, SopD, and SopE2 contribute to salmonella enterica serotype typhimurium invasion of epithelial cells. Infect Immun. 2005; 73(1): 146-154.
- 62Fattinger SA, Sellin ME, Hardt WD. Salmonella effector driven invasion of the gut epithelium: breaking in and setting the house on fire. Curr Opin Microbiol. 2021; 64: 9-18.
- 63Lian H, Jiang K, Tong M, et al. The salmonella effector protein SopD targets Rab8 to positively and negatively modulate the inflammatory response. Nat Microbiol. 2021; 6(5): 658-671.
- 64McGhie EJ, Hayward RD, Koronakis V. Cooperation between Actin-binding proteins of invasive salmonella: SipA potentiates SipC nucleation and bundling of Actin. EMBO J. 2001; 20(9): 2131-2139.
- 65Demeter A, Jacomin AC, Gul L, et al. Computational prediction and experimental validation of salmonella Typhimurium SopE-mediated fine-tuning of autophagy in intestinal epithelial cells. Front Cell Infect Microbiol. 2022; 12:834895.
- 66Lau N, Haeberle AL, O'Keeffe BJ, et al. SopF, a phosphoinositide binding effector, promotes the stability of the nascent salmonella-containing vacuole. PLoS Pathog. 2019; 15(7):e1007959.
- 67Yuan H, Zhou L, Chen Y, et al. Salmonella effector SopF regulates PANoptosis of intestinal epithelial cells to aggravate systemic infection. Gut Microbes. 2023; 15(1):2180315.
- 68Cheng S, Wang L, Liu Q, et al. Identification of a novel salmonella type III effector by quantitative Secretome profiling. Mol Cell Proteomics. 2017; 16(12): 2219-2228.
- 69Xu Y, Zhou P, Cheng S, et al. A bacterial effector reveals the V-ATPase-ATG16L1 Axis that initiates Xenophagy. Cell. 2019; 178(3): 552-566.e520.
- 70Sellin ME, Müller AA, Felmy B, et al. Epithelium-intrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion to restrict salmonella replication in the intestinal mucosa. Cell Host Microbe. 2014; 16(2): 237-248.
- 71Rauch I, Deets KA, Ji DX, et al. NAIP-NLRC4 Inflammasomes coordinate intestinal epithelial cell expulsion with eicosanoid and IL-18 release via activation of Caspase-1 and -8. Immunity. 2017; 46(4): 649-659.
- 72Fattinger SA, Geiser P, Samperio Ventayol P, et al. Epithelium-autonomous NAIP/NLRC4 prevents TNF-driven inflammatory destruction of the gut epithelial barrier in salmonella-infected mice. Mucosal Immunol. 2021; 14(3): 615-629.
- 73Broz P. Getting rid of the bad apple: inflammasome-induced extrusion of salmonella-infected enterocytes. Cell Host Microbe. 2014; 16(2): 153-155.
- 74Samperio Ventayol P, Geiser P, Di Martino ML, et al. Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers. Proc Natl Acad Sci U S A. 2021; 118(16):e2013963118.
- 75Hefele M, Stolzer I, Ruder B, et al. Intestinal epithelial Caspase-8 signaling is essential to prevent necroptosis during salmonella Typhimurium induced enteritis. Mucosal Immunol. 2018; 11(4): 1191-1202.
- 76Rhinehart E, Smith NE, Wennersten C, et al. Rapid dissemination of beta-lactamase-producing, aminoglycoside-resistant Enterococcus faecalis among patients and staff on an infant-toddler surgical ward. N Engl J Med. 1990; 323(26): 1814-1818.
- 77Chi D, Lin X, Meng Q, Tan J, Gong Q, Tong Z. Real-time induction of macrophage apoptosis, Pyroptosis, and necroptosis by Enterococcus faecalis OG1RF and two root canal isolated strains. Front Cell Infect Microbiol. 2021; 11:720147.
- 78Chi D, Zhang Y, Lin X, Gong Q, Tong Z. Caspase-1 inhibition reduces occurrence of PANoptosis in macrophages infected by E. faecalis OG1RF. J Clin Med. 2022; 11(20):6204.
- 79Rôças IN, Alves FR, Santos AL, Rosado AS, Siqueira JF Jr. Apical root canal microbiota as determined by reverse-capture checkerboard analysis of cryogenically ground root samples from teeth with apical periodontitis. J Endod. 2010; 36(10): 1617-1621.
- 80Liu H, Liu Y, Fan W, Fan B. Fusobacterium nucleatum triggers proinflammatory cell death via Z-DNA binding protein 1 in apical periodontitis. Cell Commun Signal. 2022; 20(1): 196.
- 81Martinho FC, Chiesa WM, Leite FR, Cirelli JA, Gomes BP. Antigenic activity of bacterial endodontic contents from primary root canal infection with periapical lesions against macrophage in the release of interleukin-1beta and tumor necrosis factor alpha. J Endod. 2010; 36(9): 1467-1474.
- 82Kayagaki N, Kornfeld OS, Lee BL, et al. NINJ1 mediates plasma membrane rupture during lytic cell death. Nature. 2021; 591(7848): 131-136.
- 83Brown L, Leck AK, Gichangi M, Burton MJ, Denning DW. The global incidence and diagnosis of fungal keratitis. Lancet Infect Dis. 2021; 21(3): e49-e57.
- 84Xu X, Wei Y, Pang J, et al. Time-course transcriptomic analysis reveals the crucial roles of PANoptosis in fungal keratitis. Invest Ophthalmol Vis Sci. 2023; 64(3): 6.
- 85Kesavardhana S, Malireddi RKS, Burton AR, et al. The Zα2 domain of ZBP1 is a molecular switch regulating influenza-induced PANoptosis and perinatal lethality during development. J Biol Chem. 2020; 295(24): 8325-8330.
- 86Sette A, Crotty S. Immunological memory to SARS-CoV-2 infection and COVID-19 vaccines. Immunol Rev. 2022; 310(1): 27-46.
- 87Blanco-Melo D, Nilsson-Payant BE, Liu WC, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020; 181(5): 1036-1045.e1039.
- 88Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020; 383(23): 2255-2273.
- 89Karki R, Lee S, Mall R, et al. ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection. Sci Immunol. 2022; 7(74):eabo6294.
- 90Ovsyannikova IG, Haralambieva IH, Crooke SN, Poland GA, Kennedy RB. The role of host genetics in the immune response to SARS-CoV-2 and COVID-19 susceptibility and severity. Immunol Rev. 2020; 296(1): 205-219.
- 91Le Gars M, Hendriks J, Sadoff J, et al. Immunogenicity and efficacy of Ad26.COV2.S: an adenoviral vector-based COVID-19 vaccine. Immunol Rev. 2022; 310(1): 47-60.
- 92Goldblatt D, Alter G, Crotty S, Plotkin SA. Correlates of protection against SARS-CoV-2 infection and COVID-19 disease. Immunol Rev. 2022; 310(1): 6-26.
- 93Zheng M, Williams EP, Malireddi RKS, et al. Impaired NLRP3 inflammasome activation/pyroptosis leads to robust inflammatory cell death via caspase-8/RIPK3 during coronavirus infection. J Biol Chem. 2020; 295(41): 14040-14052.
- 94Chiale C, Greene TT, Zuniga EI. Interferon induction, evasion, and paradoxical roles during SARS-CoV-2 infection. Immunol Rev. 2022; 309(1): 12-24.
- 95Palacios Y, Ramón-Luing LA, Ruiz A, et al. COVID-19 patients with high TNF/IFN-γ levels show hallmarks of PANoptosis, an inflammatory cell death. Microbes Infect. 2023; 105179: 105179.
10.1016/j.micinf.2023.105179 Google Scholar
- 96Zhang X, Yang Z, Pan T, et al. SARS-CoV-2 ORF3a induces RETREG1/FAM134B-dependent reticulophagy and triggers sequential ER stress and inflammatory responses during SARS-CoV-2 infection. Autophagy. 2022; 18(11): 2576-2592.
- 97Wei J, Alfajaro MM, DeWeirdt PC, et al. Genome-wide CRISPR screens reveal host factors critical for SARS-CoV-2 infection. Cell. 2021; 184(1): 76-91.e13.
- 98Frank MG, Nguyen KH, Ball JB, et al. SARS-CoV-2 spike S1 subunit induces neuroinflammatory, microglial and behavioral sickness responses: evidence of PAMP-like properties. Brain Behav Immun. 2022; 100: 267-277.
- 99Kwak MS, Choi S, Kim J, et al. SARS-CoV-2 infection induces HMGB1 secretion through post-translational modification and PANoptosis. Immune Netw. 2023; 23(3):e26.
- 100Jiang C, Liu G, Luckhardt T, et al. Serpine 1 induces alveolar type II cell senescence through activating p53-p21-Rb pathway in fibrotic lung disease. Aging Cell. 2017; 16(5): 1114-1124.
- 101Woo SR, Fuertes MB, Corrales L, et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity. 2014; 41(5): 830-842.
- 102Liu Y, Fei Y, Wang X, Yang B, Li M, Luo Z. Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity. Mol Ther. 2023; 31(7): 1938-1959.
- 103Garland KM, Sheehy TL, Wilson JT. Chemical and biomolecular strategies for STING pathway activation in cancer immunotherapy. Chem Rev. 2022; 122(6): 5977-6039.
- 104Liu Y, Crowe WN, Wang L, et al. An inhalable nanoparticulate STING agonist synergizes with radiotherapy to confer long-term control of lung metastases. Nat Commun. 2019; 10(1): 5108.
- 105Hanson MC, Crespo MP, Abraham W, et al. Nanoparticulate STING agonists are potent lymph node-targeted vaccine adjuvants. J Clin Invest. 2015; 125(6): 2532-2546.
- 106Nascimento M, Gombault A, Lacerda-Queiroz N, et al. Self-DNA release and STING-dependent sensing drives inflammation to cigarette smoke in mice. Sci Rep. 2019; 9(1): 14848.
- 107Benmerzoug S, Rose S, Bounab B, et al. STING-dependent sensing of self-DNA drives silica-induced lung inflammation. Nat Commun. 2018; 9(1): 5226.
- 108Messaoud-Nacer Y, Culerier E, Rose S, et al. STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome (ARDS). Cell Death Dis. 2022; 13(3): 269.
- 109Harris AJ, Mirchandani AS, Lynch RW, et al. IL4Rα signaling abrogates hypoxic neutrophil survival and limits acute lung injury responses In vivo. Am J Respir Crit Care Med. 2019; 200(2): 235-246.
- 110Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020; 20(6): 363-374.
- 111Vohwinkel CU, Coit EJ, Burns N, et al. Targeting alveolar-specific succinate dehydrogenase a attenuates pulmonary inflammation during acute lung injury. FASEB J. 2021; 35(4):e21468.
- 112Cui Y, Wang X, Lin F, et al. MiR-29a-3p improves acute lung injury by reducing alveolar epithelial cell PANoptosis. Aging Dis. 2022; 13(3): 899-909.
- 113Tian Y, Xiao H, Yang Y, et al. Crosstalk between 5-methylcytosine and N(6)-methyladenosine machinery defines disease progression, therapeutic response and pharmacogenomic landscape in hepatocellular carcinoma. Mol Cancer. 2023; 22(1): 5.
- 114Alarcón CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF. N6-methyladenosine marks primary microRNAs for processing. Nature. 2015; 519(7544): 482-485.
- 115Guo J, Luo Y, Zuo J, Teng J, Shen B, Liu X. Echinacea polyphenols inhibit NLRP3-dependent Pyroptosis, apoptosis, and necroptosis via suppressing NO production during lipopolysaccharide-induced acute lung injury. J Agric Food Chem. 2023; 71(19): 7289-7298.
- 116Wang J, Zhu Q, Wang Y, Peng J, Shao L, Li X. Irisin protects against sepsis-associated encephalopathy by suppressing ferroptosis via activation of the Nrf2/GPX4 signal axis. Free Radic Biol Med. 2022; 187: 171-184.
- 117Zhou R, Ying J, Qiu X, et al. A new cell death program regulated by toll-like receptor 9 through p38 mitogen-activated protein kinase signaling pathway in a neonatal rat model with sepsis associated encephalopathy. Chin Med J (Engl). 2022; 135(12): 1474-1485.
- 118Furie RA, van Vollenhoven RF, Kalunian K, et al. Trial of anti-BDCA2 antibody Litifilimab for systemic lupus erythematosus. N Engl J Med. 2022; 387(10): 894-904.
- 119Mistry P, Kaplan MJ. Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis. Clin Immunol. 2017; 185: 59-73.
- 120Erazo-Martínez V, Tobón GJ, Cañas CA. Circulating and skin biopsy-present cytokines related to the pathogenesis of cutaneous lupus erythematosus. Autoimmun Rev. 2023; 22(2):103262.
- 121Ghorbaninezhad F, Leone P, Alemohammad H, et al. Tumor necrosis factor-α in systemic lupus erythematosus: structure, function and therapeutic implications (review). Int J Mol Med. 2022; 49(4):43.
- 122Merrill JT, Shanahan WR, Scheinberg M, Kalunian KC, Wofsy D, Martin RS. Phase III trial results with blisibimod, a selective inhibitor of B-cell activating factor, in subjects with systemic lupus erythematosus (SLE): results from a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2018; 77(6): 883-889.
- 123Jiang J, Zhao M, Chang C, Wu H, Lu Q. Type I interferons in the pathogenesis and treatment of autoimmune diseases. Clin Rev Allergy Immunol. 2020; 59(2): 248-272.
- 124Dörner T, Tanaka Y, Petri MA, et al. Baricitinib-associated changes in global gene expression during a 24-week phase II clinical systemic lupus erythematosus trial implicates a mechanism of action through multiple immune-related pathways. Lupus Sci Med. 2020; 7(1): e000424.
- 125Sun W, Li P, Wang M, et al. Molecular characterization of PANoptosis-related genes with features of immune dysregulation in systemic lupus erythematosus. Clin Immunol. 2023; 253:109660.
- 126Chodisetti SB, Fike AJ, Domeier PP, et al. Type II but not type I IFN signaling is indispensable for TLR7-promoted development of autoreactive B cells and systemic autoimmunity. J Immunol. 2020; 204(4): 796-809.
- 127Chen P, Vu T, Narayanan A, et al. Pharmacokinetic and pharmacodynamic relationship of AMG 811, an anti-IFN-γ IgG1 monoclonal antibody, in patients with systemic lupus erythematosus. Pharm Res. 2015; 32(2): 640-653.
- 128Sun Y, Zhu C. Potential role of PANoptosis in neuronal cell death: commentary on "PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons". Neural Regen Res. 2023; 18(2): 339-340.
- 129Yan WT, Yang YD, Hu XM, et al. Do pyroptosis, apoptosis, and necroptosis (PANoptosis) exist in cerebral ischemia? Evidence from cell and rodent studies. Neural Regen Res. 2022; 17(8): 1761-1768.
- 130Uysal E, Dokur M, Kucukdurmaz F, et al. Targeting the PANoptosome with 3,4-Methylenedioxy-β-Nitrostyrene, reduces PANoptosis and protects the kidney against renal İschemia-reperfusion injury. J Invest Surg. 2022; 35(11–12): 1824-1835.
- 131Mi XS, Feng Q, Lo ACY, Chang RC, Chung SK, So KF. Lycium barbarum polysaccharides related RAGE and Aβ levels in the retina of mice with acute ocular hypertension and promote maintenance of blood retinal barrier. Neural Regen Res. 2020; 15(12): 2344-2352.
- 132Yao F, Peng J, Zhang E, et al. Pathologically high intraocular pressure disturbs normal iron homeostasis and leads to retinal ganglion cell ferroptosis in glaucoma. Cell Death Differ. 2023; 30(1): 69-81.
- 133Kleele T, Rey T, Winter J, et al. Distinct fission signatures predict mitochondrial degradation or biogenesis. Nature. 2021; 593(7859): 435-439.
- 134Kim KY, Perkins GA, Shim MS, et al. DRP1 inhibition rescues retinal ganglion cells and their axons by preserving mitochondrial integrity in a mouse model of glaucoma. Cell Death Dis. 2015; 6(8):e1839.
- 135Zeng Z, You M, Fan C, Rong R, Li H, Xia X. Pathologically high intraocular pressure induces mitochondrial dysfunction through Drp1 and leads to retinal ganglion cell PANoptosis in glaucoma. Redox Biol. 2023; 62:102687.
- 136Ye D, Xu Y, Shi Y, et al. Anti-PANoptosis is involved in neuroprotective effects of melatonin in acute ocular hypertension model. J Pineal Res. 2022; 73(4):e12828.
- 137Yi X, Li J, Zheng X, et al. Construction of PANoptosis signature: novel target discovery for prostate cancer immunotherapy. Molecular Therapy - Nucleic Acids. 2023; 33: 376-390.
- 138Fujita T, Reis LF, Watanabe N, Kimura Y, Taniguchi T, Vilcek J. Induction of the transcription factor IRF-1 and interferon-beta mRNAs by cytokines and activators of second-messenger pathways. Proc Natl Acad Sci U S A. 1989; 86(24): 9936-9940.
- 139Bouker KB, Skaar TC, Riggins RB, et al. Interferon regulatory factor-1 (IRF-1) exhibits tumor suppressor activities in breast cancer associated with caspase activation and induction of apoptosis. Carcinogenesis. 2005; 26(9): 1527-1535.
- 140Kamijo R, Harada H, Matsuyama T, et al. Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science. 1994; 263(5153): 1612-1615.
- 141Man SM, Karki R, Malireddi RK, et al. The transcription factor IRF1 and guanylate-binding proteins target activation of the AIM2 inflammasome by Francisella infection. Nat Immunol. 2015; 16(5): 467-475.
- 142Buch T, Uthoff-Hachenberg C, Waisman A. Protection from autoimmune brain inflammation in mice lacking IFN-regulatory factor-1 is associated with Th2-type cytokines. Int Immunol. 2003; 15(7): 855-859.
- 143Nakazawa T, Satoh J, Takahashi K, et al. Complete suppression of insulitis and diabetes in NOD mice lacking interferon regulatory factor-1. J Autoimmun. 2001; 17(2): 119-125.
- 144Pfister D, Núñez NG, Pinyol R, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature. 2021; 592(7854): 450-456.
- 145Kakiuchi N, Yoshida K, Uchino M, et al. Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis. Nature. 2020; 577(7789): 260-265.
- 146Conlon TM, John-Schuster G, Heide D, et al. Inhibition of LTβR signalling activates WNT-induced regeneration in lung. Nature. 2020; 588(7836): 151-156.
- 147Tamura G, Ogasawara S, Nishizuka S, et al. Two distinct regions of deletion on the long arm of chromosome 5 in differentiated adenocarcinomas of the stomach. Cancer Res. 1996; 56(3): 612-615.
- 148Ogasawara S, Tamura G, Maesawa C, et al. Common deleted region on the long arm of chromosome 5 in esophageal carcinoma. Gastroenterology. 1996; 110(1): 52-57.
- 149Sharma BR, Karki R, Rajesh Y, Kanneganti TD. Immune regulator IRF1 contributes to ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosome activation and inflammatory cell death (PANoptosis). J Biol Chem. 2023; 299(9):105141.
- 150Karki R, Sharma BR, Lee E, et al. Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer. JCI Insight. 2020; 5(12):e136720.
- 151Poulsen H, Nilsson J, Damgaard CK, Egebjerg J, Kjems J. CRM1 mediates the export of ADAR1 through a nuclear export signal within the Z-DNA binding domain. Mol Cell Biol. 2001; 21(22): 7862-7871.
- 152Taylor J, Sendino M, Gorelick AN, et al. Altered nuclear export signal recognition as a driver of Oncogenesis. Cancer Discov. 2019; 9(10): 1452-1467.
- 153Azizian NG, Li Y. XPO1-dependent nuclear export as a target for cancer therapy. J Hematol Oncol. 2020; 13(1): 61.
- 154Gravina GL, Senapedis W, McCauley D, Baloglu E, Shacham S, Festuccia C. Nucleo-cytoplasmic transport as a therapeutic target of cancer. J Hematol Oncol. 2014; 7: 85.
- 155Chari A, Vogl DT, Gavriatopoulou M, et al. Oral Selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019; 381(8): 727-738.
- 156Camilli S, Lockey R, Kolliputi N. Nuclear export inhibitors Selinexor (KPT-330) and Eltanexor (KPT-8602) provide a novel therapy to reduce tumor growth by induction of PANoptosis. Cell Biochem Biophys. 2023; 81: 421-426.
- 157Kanemitsu Y, Shitara K, Mizusawa J, et al. Primary tumor resection plus chemotherapy versus chemotherapy alone for colorectal cancer patients with asymptomatic, synchronous Unresectable metastases (JCOG1007; iPACS): a randomized clinical trial. J Clin Oncol. 2021; 39(10): 1098-1107.
- 158Ychou M, Rivoire M, Thezenas S, et al. Chemotherapy (doublet or triplet) plus targeted therapy by RAS status as conversion therapy in colorectal cancer patients with initially unresectable liver-only metastases. The UNICANCER PRODIGE-14 randomised clinical trial. Br J Cancer. 2022; 126(9): 1264-1270.
- 159Tan Y, Li J, Zhao G, et al. Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells. Nat Commun. 2022; 13(1): 4554.
- 160Boroughs LK, DeBerardinis RJ. Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol. 2015; 17(4): 351-359.
- 161Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression. Science. 2020; 368: 6487.
- 162Ju HQ, Lin JF, Tian T, Xie D, Xu RH. NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications. Signal Transduct Target Ther. 2020; 5(1): 231.
- 163Solanki S, Sanchez K, Ponnusamy V, et al. Dysregulated amino acid sensing drives colorectal cancer growth and metabolic reprogramming leading to Chemoresistance. Gastroenterology. 2023; 164(3): 376-391.e313.
- 164Ma S, Sun B, Duan S, et al. YTHDF2 orchestrates tumor-associated macrophage reprogramming and controls antitumor immunity through CD8(+) T cells. Nat Immunol. 2023; 24(2): 255-266.
- 165Li G, Choi JE, Kryczek I, et al. Intersection of immune and oncometabolic pathways drives cancer hyperprogression during immunotherapy. Cancer Cell. 2023; 41(2): 304-322.e307.
- 166Raggi C, Taddei ML, Sacco E, et al. Mitochondrial oxidative metabolism contributes to a cancer stem cell phenotype in cholangiocarcinoma. J Hepatol. 2021; 74(6): 1373-1385.
- 167Alvarez SW, Sviderskiy VO, Terzi EM, et al. NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature. 2017; 551(7682): 639-643.
- 168Ward NP, Kang YP, Falzone A, Boyle TA, DeNicola GM. Nicotinamide nucleotide transhydrogenase regulates mitochondrial metabolism in NSCLC through maintenance of Fe-S protein function. J Exp Med. 2020; 217(6):e20191689.
- 169Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020; 21(7): 363-383.
- 170O'Brien ME, Wigler N, Inbar M, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004; 15(3): 440-449.
- 171Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of intergroup trial C9741/cancer and leukemia group B trial 9741. J Clin Oncol. 2003; 21(8): 1431-1439.
- 172Aix SP, Ciuleanu TE, Navarro A, et al. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023; 11(1): 74-86.
- 173Lu D, Chatterjee S, Xiao K, et al. A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity. Eur Heart J. 2022; 43(42): 4496-4511.
- 174Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015; 131(22): 1981-1988.
- 175Tomczyk MM, Cheung KG, Xiang B, et al. Mitochondrial Sirtuin-3 (SIRT3) prevents doxorubicin-induced dilated cardiomyopathy by modulating protein acetylation and oxidative stress. Circ Heart Fail. 2022; 15(5):e008547.
- 176Carvalho FS, Burgeiro A, Garcia R, Moreno AJ, Carvalho RA, Oliveira PJ. Doxorubicin-induced cardiotoxicity: from bioenergetic failure and cell death to cardiomyopathy. Med Res Rev. 2014; 34(1): 106-135.
- 177Wu L, Wang L, Du Y, Zhang Y, Ren J. Mitochondrial quality control mechanisms as therapeutic targets in doxorubicin-induced cardiotoxicity. Trends Pharmacol Sci. 2023; 44(1): 34-49.
- 178Bi Y, Xu H, Wang X, et al. FUNDC1 protects against doxorubicin-induced cardiomyocyte PANoptosis through stabilizing mtDNA via interaction with TUFM. Cell Death Dis. 2022; 13(12): 1020.
- 179Liu L, Feng D, Chen G, et al. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol. 2012; 14(2): 177-185.
- 180Wang C, Dai X, Wu S, Xu W, Song P, Huang K. FUNDC1-dependent mitochondria-associated endoplasmic reticulum membranes are involved in angiogenesis and neoangiogenesis. Nat Commun. 2021; 12(1): 2616.
- 181Pei Z, Liu Y, Liu S, et al. FUNDC1 insufficiency sensitizes high fat diet intake-induced cardiac remodeling and contractile anomaly through ACSL4-mediated ferroptosis. Metabolism. 2021; 122:154840.
- 182Li J, Agarwal E, Bertolini I, et al. The mitophagy effector FUNDC1 controls mitochondrial reprogramming and cellular plasticity in cancer cells. Sci Signal. 2020; 13(642):eaaz8240.
- 183Ren J, Sun M, Zhou H, et al. FUNDC1 interacts with FBXL2 to govern mitochondrial integrity and cardiac function through an IP3R3-dependent manner in obesity. Sci Adv. 2020; 6(38):eabc8561.
- 184Song M, Xia W, Tao Z, et al. Self-assembled polymeric nanocarrier-mediated co-delivery of metformin and doxorubicin for melanoma therapy. Drug Deliv. 2021; 28(1): 594-606.
- 185Benfield P, Clissold SP. Sulconazole. A review of its antimicrobial activity and therapeutic use in superficial dermatomycoses. Drugs. 1988; 35(2): 143-153.
- 186Yoon J, Grinchuk OV, Kannan S, et al. A chemical biology approach reveals a dependency of glioblastoma on biotin distribution. Sci Adv. 2021; 7(36):eabf6033.
- 187Choi HS, Kim JH, Kim SL, Lee DS. Disruption of the NF-κB/IL-8 signaling Axis by Sulconazole inhibits human breast cancer stem cell formation. Cell. 2019; 8(9):1007.
- 188Liu LX, Heng JH, Deng DX, et al. Sulconazole induces PANoptosis by triggering oxidative stress and inhibiting glycolysis to increase Radiosensitivity in esophageal cancer. Mol Cell Proteomics. 2023; 22(6):100551.
- 189Zhou L, Lyu J, Liu F, Su Y, Feng L, Zhang X. Immunogenic PANoptosis-initiated cancer Sono-immune reediting Nanotherapy by iteratively boosting cancer immunity cycle. Adv Mater. 2023;e2305361.
- 190Wang Y, Pandian N, Han JH, et al. Single cell analysis of PANoptosome cell death complexes through an expansion microscopy method. Cell Mol Life Sci. 2022; 79(10): 531.
- 191Tong J, Lan XT, Zhang Z, et al. Ferroptosis inhibitor liproxstatin-1 alleviates metabolic dysfunction-associated fatty liver disease in mice: potential involvement of PANoptosis. Acta Pharmacol Sin. 2023; 44(5): 1014-1028.
Citing Literature
