Inflammasome and immune disorders

Viral protease-Initiated Pyroptosis Activator mRNA therapy as a Universal Antiviral Strategy

This paper develops VIPA mRNA therapy, which uses viral protease-initiated pyroptosis to suppress viral replication and elicit immune responses in animal models.

Cleavage of the Hippo kinases and programmed cell death in murine macrophages exposed to sterile stimuli and bacterial pathogens

This study shows that MST1/2 cleavage in macrophages mediates programmed cell death in response to sterile stimuli and bacterial pathogens, with distinct pathways depending on inflammasome activation.

Human Norovirus NS7 Protein Activates Canonical Inflammasome Pathways via NLRP6 in Intestinal Epithelial Cells

This study identifies the HNoV NS7 protein as a direct activator of NLRP6 and NLRP3 inflammasomes in intestinal epithelial cells, revealing NLRP6's critical role in antiviral defense against norovirus.

The atypical filament assembly underpins the inflammasome-independent functions of IFI16.

This study reveals the structural basis for IFI16's inflammasome-independent functions through cryo-EM and computational analysis of its unique filament assembly.

Evolution of a Pyroptosis-Apoptosis crosstalk drives non-canonical inflammasome signalling.

This study identifies a novel mechanism by which caspase-4 and -5 interact with executioner caspases-3 and -7 to enable pyroptosis-apoptosis crosstalk, enhancing inflammatory responses.

Chronic sensing of host-derived lipids is an all-in-one signal that primes and activates NLRP3.

The paper shows that chronic exposure to oxidized phospholipids primes and activates NLRP3 via NRF2, independent of microbial cues, contributing to atherogenesis.

Modulating NLRP3 splicing with antisense oligonucleotides to control pathological inflammation

This study uses antisense oligonucleotides to modulate NLRP3 splicing, reducing its inflammatory activity and systemic inflammation in mouse models.

Non-canonical inflammasome drives intrinsic anti-microbial responses in human Natural Killer (NK) cells.

This study identifies a non-canonical inflammasome in human NK cells that mediates anti-microbial responses against Salmonella without canonical inflammasome components.

An animal model for autoinflammation with infantile enterocolitis

This study develops a conditional NLRC4 knock-in mouse model that recapitulates the clinical features of autoinflammatory enterocolitis in infants.

A caspase-1-cathepsin AND-gate probe for selectiveimaging of inflammasome activation

The paper designs a caspase-1-cathepsin AND-gate probe to selectively image inflammasome activation by requiring processing by both enzymes.

The unique lipopolysaccharide composition of Salmonella Typhimurium ST313 dampens pyroptosis and inflammasome activation and suppresses host cell death

This study identifies that the unique lipopolysaccharide (LPS) of Salmonella Typhimurium ST313 reduces pyroptosis and inflammasome activation in human macrophages, contributing to its pathogenicity.

NLRP3 is a thermosensor that is negatively regulated by high temperature

This study shows high temperatures inhibit NLRP3 inflammasome activation, identifying NLRP3 as a thermosensor and revealing a temperature-sensitive conformational change in its C-terminal domain.

GBP1 recruitment to actin-rich pedestals induced by extracellular Gram-negative bacteria promotes pyroptosis.

This study shows GBP1 is recruited to actin-rich pedestals formed by extracellular pathogens, promoting pyroptosis and IL-18 release, independent of LPS.

Staphylococcus aureus inhibits the NLRP3 inflammasome in macrophages during the early phases of intracellular infection, but not the late phases

This study shows S. aureus inhibits NLRP3 inflammasome activation in macrophages during early infection but not late infection, reducing bacterial load and pyroptosis.

Expression of Intron-containing HIV-1 RNA Induces NLRP1 Inflammasome Activation in Myeloid Cells

This study shows that HIV-1 intron-containing RNA induces NLRP1 inflammasome activation and IL-1β secretion in myeloid cells through a RLR- and endosomal TLR-independent mechanism.

Induced pluripotent stem cell-derived macrophages as a model for human inflammasome signaling

This study generates and benchmarks iPSC-derived macrophages (iMacs) as a model for human inflammasome signaling, showing they respond to multiple inflammasome stimuli and activate unique pathways.

Inflammasomes and DNA Damage Orchestrate Divergent Pyroptotic Fates in Neutrophils

This study investigates pyroptotic responses in neutrophils under different conditions, revealing distinct mechanisms involving inflammasomes, DNA damage, and actomyosin forces that determine cytokine secretion or cell death.

Clarifying the priming requirement and activator specificity for the NLRP3 inflammasome in human keratinocytes in vitro

This study investigates NLRP3 inflammasome activation in human keratinocytes, showing it is induced by IFN-gamma but not LPS, and that specific activators like Hla target NLRP3 while nigericin activates both NLRP1 and NLRP3.

Optimizing PDIA1 Inhibition as a Strategy to Inhibit NLRP3 Inflammasome Activation and Activity

This study identifies potent PDIA1 inhibitors that block NLRP3 inflammasome activity without significant cellular toxicity, offering a strategy to treat diseases involving hyperactive NLRP3.

NLRP3 inflammasome is regulated in osteoclasts through a Tmem178-dependent mechanism that restricts calcium influx

The paper shows Tmem178 suppresses NLRP3 inflammasome activation in osteoclasts by limiting calcium release, preventing excessive bone resorption.

Discovery of a Potent and Selective Inhibitor of Human NLRP3 with a Novel Binding Modality and Mechanism of Action

This paper characterizes BAL-0028, a novel NLRP3 inhibitor with a distinct binding site and mechanism, showing potent inhibition of human and primate NLRP3 and efficacy in a peritonitis model.

Paraquat Licences α-Synuclein to Trigger NLRP3-Dependent Pyroptosis in Microglia

This study shows paraquat enables α-synuclein to trigger NLRP3-dependent pyroptosis in microglia, linking environmental toxins to Parkinson's disease pathogenesis.

Cardiolipin Inhibits the Noncanonical Inflammasome by Preventing LPS Binding to Caspase 4/11 to Mitigate Endotoxemia in Vivo

This study identifies cardiolipin as a selective inhibitor of caspase 4/11 that prevents LPS-induced inflammation without affecting caspase-1, offering a potential therapeutic for Gram-negative sepsis.

Stress granule component TIA-1 is a specific negative regulator of the non-canonical NLRP3 inflammasome.

This study identifies TIA-1 as a negative regulator of the non-canonical NLRP3 inflammasome, showing its role in suppressing LPS-induced inflammation and endotoxic shock.

The cytoplasmic scaffolding protein PCNA as a new regulator of activation of the classical NRLP3 inflammasome

This study identifies PCNA as a cytoplasmic regulator of NLRP3 inflammasome activation by interacting with NEK7 and modulating inflammasome-mediated cytokine secretion and pyroptosis.

Inhibition of NLRP3 by a CNS-penetrating indazole scaffold

This paper identifies and characterizes BAL-1516, a CNS-penetrating NLRP3 inhibitor that blocks inflammasome formation and shows potential for treating neuroinflammatory diseases.

A cereblon (CRBN) molecular glue degrader of NIMA-related kinase 7 (NEK7) reveals a context-dependent role in NLRP3 inflammasome activation

This paper identifies NK7-902, a CRBN molecular glue degrader of NEK7, showing partial inhibition of NLRP3 inflammasome activation in humans and full activity in mice, but only transient effects in non-human primates.

Large-Scale Restructuring of the Caspase-1 Gene Cluster Region in Mammals

The paper examines the evolution of the NLRP3 inflammasome pathway genes across mammals, revealing chromosomal reorganization and gene duplication events, particularly in Caspase-1 and neighboring genes.

Env from EIAV vaccine delicately regulates NLRP3 activation via attenuating NLRP3-NEK7 interaction

This study identifies how EIAV vaccine Env regulates NLRP3 inflammasome activation by reducing NLRP3-NEK7 complex formation while preserving P2X7-mediated ion flux.

CARD8 inflammasome activation during HIV-1 cell-to-cell transmission

The paper investigates CARD8 inflammasome activation during HIV-1 cell-to-cell transmission, showing it depends on viral protease activity and not NLRP3.