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Inflammasome and immune disorders
Research Guide
What is Inflammasome and immune disorders?
The inflammasome is a multiprotein complex that activates inflammatory responses through caspase-1-mediated processing of interleukin-1 and induction of pyroptosis, with dysregulation contributing to immune disorders such as autoinflammatory diseases.
This field encompasses 49,582 papers on molecular mechanisms of inflammasome activation, regulation, pyroptosis, and roles in immune-related diseases. Key components include NLRP3 inflammasome, interleukin-1, caspase-1, and mitochondrial involvement in activation. Research links inflammasome activity to inflammatory conditions like atherosclerosis and cancer.
Topic Hierarchy
Research Sub-Topics
NLRP3 Inflammasome Activation Mechanisms
This sub-topic dissects the multi-step process of NLRP3 activation involving potassium efflux, lysosomal damage, and mitochondrial ROS signaling. Researchers identify novel sensors and posttranslational modifications regulating inflammasome priming and assembly.
Pyroptosis and Gasdermin Biology
Focuses on caspase-mediated cleavage of gasdermin D forming membrane pores that execute lytic cell death and release inflammatory DAMPs. Studies explore non-canonical pyroptosis via caspase-11/4 and gasdermin family redundancy.
Caspase-1 Structure and Regulation
Examines the inflammasome-induced dimerization and autocatalytic activation of caspase-1, including allosteric regulation and inhibitor design. Researchers use cryo-EM structures to develop selective inhibitors blocking IL-1β processing.
Mitochondrial Regulation of Inflammasomes
Investigates mitochondria-derived danger signals like mtDNA, cardiolipin, and ROS that trigger NLRP3 assembly at mitochondrial surfaces. Studies elucidate mitophagy defects enhancing inflammasome hyperactivation in chronic disease.
Inflammasome Therapeutics and Inhibitors
This area evaluates small molecules, biologics, and gene therapies targeting inflammasome components in clinical trials for autoinflammatory diseases. Research addresses selectivity challenges distinguishing pathogenic from homeostatic inflammasome activity.
Why It Matters
Inflammasome dysregulation drives immune disorders including atherosclerosis and cardiovascular disease. "Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease" by Ridker et al. (2017) showed that canakinumab at 150 mg every 3 months reduced recurrent cardiovascular events by targeting the interleukin-1β pathway, independent of lipid lowering, in the CANTOS trial. "Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death" by Shi et al. (2015) identified GSDMD cleavage as the executor of pyroptosis, a mechanism central to inflammatory cell death in immune disorders. These findings support therapeutic targeting of inflammasomes in autoinflammatory diseases and cancer, as explored in "Inflammation and cancer: back to Virchow?" by Balkwill and Mantovani (2001).
Reading Guide
Where to Start
"The Inflammasome" by Martinon et al. (2002), as it provides the foundational description of inflammasome structure and function essential for understanding activation in immune disorders.
Key Papers Explained
"The Inflammasome" by Martinon et al. (2002) introduced the complex and its role in interleukin-1 processing. "Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death" by Shi et al. (2015) built on this by detailing pyroptosis execution via GSDMD. "Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease" by Ridker et al. (2017) applied these mechanisms clinically, showing interleukin-1β inhibition reduces cardiovascular events. "Inflammation, Atherosclerosis, and Coronary Artery Disease" by Hansson (2005) connected inflammation to disease pathogenesis. "Pattern Recognition Receptors and Inflammation" by Takeuchi and Akira (2010) explained upstream signals leading to inflammasome assembly.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Research centers on NLRP3 regulation, pyroptosis mechanisms, and therapeutic targeting of interleukin-1 in immune disorders, as in top-cited works; no recent preprints indicate focus remains on established pathways like GSDMD and caspase-1.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Inflammation, Atherosclerosis, and Coronary Artery Disease | 2005 | New England Journal of... | 8.6K | ✕ |
| 2 | Antiinflammatory Therapy with Canakinumab for Atherosclerotic ... | 2017 | New England Journal of... | 8.6K | ✓ |
| 3 | Pattern Recognition Receptors and Inflammation | 2010 | Cell | 8.4K | ✓ |
| 4 | NF-κB signaling in inflammation | 2017 | Signal Transduction an... | 7.7K | ✓ |
| 5 | Inflammation and cancer: back to Virchow? | 2001 | The Lancet | 7.6K | ✕ |
| 6 | Markers of Inflammation and Cardiovascular Disease | 2003 | Circulation | 6.3K | ✓ |
| 7 | Cleavage of GSDMD by inflammatory caspases determines pyroptot... | 2015 | Nature | 6.2K | ✕ |
| 8 | Origin and physiological roles of inflammation | 2008 | Nature | 6.2K | ✕ |
| 9 | Molecular mechanisms of cell death: recommendations of the Nom... | 2018 | Cell Death and Differe... | 6.1K | ✓ |
| 10 | The Inflammasome | 2002 | Molecular Cell | 5.9K | ✓ |
Frequently Asked Questions
What is the inflammasome?
The inflammasome is a multiprotein complex that activates caspase-1 to process pro-interleukin-1β into its mature form and induce pyroptosis. "The Inflammasome" by Martinon et al. (2002) described its assembly and role in innate immunity. This complex responds to microbial and damage signals in immune disorders.
How does pyroptosis occur in inflammasome activation?
Inflammatory caspases cleave gasdermin D (GSDMD) to form membrane pores that execute pyroptotic cell death. "Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death" by Shi et al. (2015) demonstrated that GSDMD N-terminal fragments disrupt plasma membranes. This process amplifies inflammation in immune disorders.
What role does interleukin-1 play in inflammasome-related diseases?
Interleukin-1β, processed by inflammasome-activated caspase-1, drives inflammatory responses in diseases like atherosclerosis. "Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease" by Ridker et al. (2017) showed canakinumab targeting interleukin-1β reduced cardiovascular events. This pathway links inflammasomes to autoinflammatory conditions.
How are pattern recognition receptors involved in inflammasome activation?
Pattern recognition receptors detect microbial patterns and damage signals to trigger inflammasome assembly. "Pattern Recognition Receptors and Inflammation" by Takeuchi and Akira (2010) outlined their role in initiating inflammatory cascades. These receptors connect innate immunity to NLRP3 inflammasome responses in immune disorders.
What is the connection between inflammation and atherosclerosis?
Inflammation promotes atherosclerosis through cytokine-driven plaque formation. "Inflammation, Atherosclerosis, and Coronary Artery Disease" by Hansson (2005) summarized how immune responses contribute to acute coronary syndromes. Inflammasome activation exacerbates this process via interleukin-1.
What defines the current state of inflammasome research?
The field includes 49,582 works focusing on NLRP3, pyroptosis, and diseases like autoinflammatory disorders. Key papers define mechanisms such as GSDMD cleavage and therapeutic inhibition. No recent preprints or news coverage indicate stable foundational research.
Open Research Questions
- ? How do mitochondrial signals precisely regulate NLRP3 inflammasome activation in autoinflammatory diseases?
- ? What are the specific upstream regulators of GSDMD cleavage beyond caspase-1 in pyroptosis?
- ? Can inflammasome inhibitors like canakinumab be optimized for broader immune disorders beyond atherosclerosis?
- ? How does NF-κB signaling interact with inflammasomes in chronic inflammation?
- ? What distinguishes pyroptosis from other cell death pathways in immune responses?
Recent Trends
The field holds steady at 49,582 papers with no reported 5-year growth data.
Highly cited works from 2002-2018, such as "Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease" by Ridker et al. with 8619 citations, continue to dominate, linking inflammasomes to clinical outcomes.
2017No recent preprints or news coverage noted.
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