Human Autoinflammatory Diseases Mediated by NLRP3-, Pyrin-, NLRP1-, and NLRC4-Inflammasome Dysregulation Updates on Diagnosis, Treatment, and the Respective Roles of IL-1 and IL-18

Generation and characterization of antagonistic anti-human interleukin (IL)-18 monoclonal antibodies with high affinity: Two types of monoclonal antibodies against full-length IL-18 and the neoepitope of inflammatory caspase-cleaved active IL-18

(2019) Yuko Nariai et al.   ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Emapalumab: First Global Approval

(2019) Zaina T. Al-Salama   DRUGS

Defying Death: The (W)hole Truth about the Fate of GSDMD Pores

(2019) Charles L. Evavold et al.   IMMUNITY

Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors

(2019) Yang Yang et al.   Cell Death & Disease

N-terminal degradation activates the NLRP1B inflammasome

(2019) Ashley J. Chui et al.   SCIENCE

Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes

(2019) Andrew Sandstrom et al.   SCIENCE

The N‐end rule ubiquitin ligase UBR2 mediates NLRP1B inflammasome activation by anthrax lethal toxin

(2019) Hao Xu et al.   EMBO JOURNAL

When Degradation Elicits the Alarm: N-Terminal Degradation of NLRP1B Unleashes Its Inflammasome Activity

(2019) Mohamed A. Eldeeb et al.   MOLECULAR CELL

An innate interaction between IL-18 and the propeptide that inactivates its precursor form

(2019) Naotaka Tsutsumi et al.   Scientific Reports

The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation

(2019) Nathan Kelley et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Severe autoinflammation in 4 patients with C-terminal variants in cell division control protein 42 homolog (CDC42) successfully treated with IL-1β inhibition

(2019) Yael Gernez et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Inherited IL-18BP deficiency in human fulminant viral hepatitis

(2019) Serkan Belkaya et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome

(2019) Humayun Sharif et al.   NATURE

Upregulation of the NLRC4 inflammasome contributes to poor prognosis in glioma patients

(2019) Jaejoon Lim et al.   Scientific Reports

Canakinumab provides rapid and sustained long‐term efficacy and safety in patients with cryopyrin‐associated periodic syndrome aged ≤5 years

(2019) Paul A Brogan et al.   Arthritis & Rheumatology

Emergent high fatality lung disease in systemic juvenile arthritis

(2019) Vivian E Saper et al.   ANNALS OF THE RHEUMATIC DISEASES

Inflammasomes: Threat-Assessment Organelles of the Innate Immune System

(2019) Charles L. Evavold et al.   IMMUNITY

Drugs to Inhibit the NLRP3 Inflammasome

(2019) Adolfo Gabriele Mauro et al.   JOURNAL OF CARDIOVASCULAR PHARMACOLOGY

Gene Mosaicism Screening Using Single-Molecule Molecular Inversion Probes in Routine Diagnostics for Systemic Autoinflammatory Diseases

(2019) Benjamin Kant et al.   JOURNAL OF MOLECULAR DIAGNOSTICS

Homozygous NLRP1 gain-of-function mutation in siblings with a syndromic form of recurrent respiratory papillomatosis

(2019) Scott B. Drutman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Storm Warning: Lung Disease in Systemic Juvenile Idiopathic Arthritis

(2019) Peter A. Nigrovic   Arthritis & Rheumatology

The Pyrin Inflammasome in Health and Disease

(2019) Oskar Schnappauf et al.   Frontiers in Immunology

Structural and mechanistic elucidation of inflammasome signaling by cryo-EM

(2019) Chen Shen et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function

(2019) Michael T. Lam et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Systemic Juvenile Idiopathic Arthritis–Associated Lung Disease: Characterization and Risk Factors

(2019) Grant S. Schulert et al.   Arthritis & Rheumatology

Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases

(2019) Adriana A. de Jesus et al.   JOURNAL OF CLINICAL INVESTIGATION

Unopposed IL-18 signaling leads to severe TLR9-induced macrophage activation syndrome in mice

(2018) Charlotte Girard-Guyonvarc’h et al.   BLOOD

Interleukin-18 diagnostically distinguishes and pathogenically promotes human and murine macrophage activation syndrome

(2018) Eric S. Weiss et al.   BLOOD

Single-cell analysis of pyroptosis dynamics reveals conserved GSDMD-mediated subcellular events that precede plasma membrane rupture

(2018) Nathalia M. de Vasconcelos et al.   CELL DEATH AND DIFFERENTIATION

Lack of clear and univocal genotype-phenotype correlation in familial Mediterranean fever patients: A systematic review

(2018) S. Gangemi et al.   CLINICAL GENETICS

Development and effect of antibodies to anakinra during treatment of severe CAPS: sub-analysis of a long-term safety and efficacy study

(2018) Margareta Wikén et al.   CLINICAL RHEUMATOLOGY

Mechanism of membrane pore formation by human gasdermin‐D

(2018) Estefania Mulvihill et al.   EMBO JOURNAL

Tranilast directly targets NLRP3 to treat inflammasome‐driven diseases

(2018) Yi Huang et al.   EMBO Molecular Medicine

The Gasdermin-D pore acts as a conduit for IL-1β secretion in mice

(2018) Rosalie Heilig et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions

(2018) Maximilien Evrard et al.   IMMUNITY

The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages

(2018) Charles L. Evavold et al.   IMMUNITY

Novel aspects of the assembly and activation of inflammasomes with focus on the NLRC4 inflammasome

(2018) William G Fusco et al.   INTERNATIONAL IMMUNOLOGY

Neutralization of IFN-γ reverts clinical and laboratory features in a mouse model of macrophage activation syndrome

(2018) Giusi Prencipe et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Autoinflammatory mutation in NLRC4 reveals a leucine-rich repeat (LRR)–LRR oligomerization interface

(2018) Fiona Moghaddas et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity

(2018) Dave Boucher et al.   JOURNAL OF EXPERIMENTAL MEDICINE

GSDMD is critical for autoinflammatory pathology in a mouse model of Familial Mediterranean Fever

(2018) Apurva Kanneganti et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Mechanisms of NLRP1-Mediated Autoinflammatory Disease in Humans and Mice

(2018) Chien-Hsiung Yu et al.   JOURNAL OF MOLECULAR BIOLOGY

Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells

(2018) Margherita Norelli et al.   NATURE MEDICINE

CAR T cell–induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade

(2018) Theodoros Giavridis et al.   NATURE MEDICINE

Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes

(2018) Fabrizio De Benedetti et al.   NEW ENGLAND JOURNAL OF MEDICINE

The safety of live-attenuated vaccines in patients using IL-1 or IL-6 blockade: an international survey

(2018) Jerold Jeyaratnam et al.   Pediatric Rheumatology

OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation

(2018) Carlo Marchetti et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The E3 ubiquitin ligase Pellino2 mediates priming of the NLRP3 inflammasome

(2018) Fiachra Humphries et al.   Nature Communications

The pyrin inflammasome: from sensing RhoA GTPases-inhibiting toxins to triggering autoinflammatory syndromes

(2018) Yvan Jamilloux et al.   Pathogens and Disease

Mosaicism in autoinflammatory diseases: Cryopyrin-associated periodic syndromes (CAPS) and beyond. A systematic review

(2018) Marielle Labrousse et al.   CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES

The role of mitochondria in NLRP3 inflammasome activation

(2018) Qiuyun Liu et al.   MOLECULAR IMMUNOLOGY

Cryo-EM structure of the gasdermin A3 membrane pore

(2018) Jianbin Ruan et al.   NATURE

New mitochondrial DNA synthesis enables NLRP3 inflammasome activation

(2018) Zhenyu Zhong et al.   NATURE

Targeting the NLRP3 inflammasome in inflammatory diseases

(2018) Matthew S. J. Mangan et al.   NATURE REVIEWS DRUG DISCOVERY

Inflammasome signalling in brain function and neurodegenerative disease

(2018) Michael T. Heneka et al.   NATURE REVIEWS NEUROSCIENCE

NLRP3 inflammasome activation in inflammaging

(2018) Eicke Latz et al.   SEMINARS IN IMMUNOLOGY

SUMO-mediated regulation of NLRP3 modulates inflammasome activity

(2018) Rachael Barry et al.   Nature Communications

Prolonged treatment with Tadekinig alfa in adult-onset Still’s disease

(2018) Uta Kiltz et al.   ANNALS OF THE RHEUMATIC DISEASES

Updates on autoinflammatory diseases

(2018) Narcisa Martinez-Quiles et al.   CURRENT OPINION IN IMMUNOLOGY

Contribution of the inflammasome to inflammaging

(2018) Nancy H. Mejias et al.   Journal of Inflammation-London

NLRP1 Is the Key Inflammasome in Primary Human Keratinocytes

(2018) Marc Burian et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation

(2018) Monica Yabal et al.   JOURNAL OF LEUKOCYTE BIOLOGY

ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation

(2018) Sebastian Rühl et al.   SCIENCE

Targeting of NLRP3 inflammasome with gene editing for the amelioration of inflammatory diseases

(2018) Congfei Xu et al.   Nature Communications

Gasdermin D mediates the pathogenesis of neonatal-onset multisystem inflammatory disease in mice

(2018) Jianqiu Xiao et al.   PLOS BIOLOGY

Hemophagocytic Lymphohistiocytosis: Clinical Presentations and Diagnosis

(2018) Kimberly A. Risma et al.   Journal of Allergy and Clinical Immunology-In Practice

Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition

(2017) Scott W. Canna et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Protein kinase D at the Golgi controls NLRP3 inflammasome activation

(2017) Zhirong Zhang et al.   JOURNAL OF EXPERIMENTAL MEDICINE

NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice

(2017) Auvro R. Mridha et al.   JOURNAL OF HEPATOLOGY

Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial

(2017) Paul M Ridker et al.   LANCET

Chimeric antigen receptor T-cell therapy — assessment and management of toxicities

(2017) Sattva S. Neelapu et al.   Nature Reviews Clinical Oncology

Novel NLRC4 Mutation Causes a Syndrome of Perinatal Autoinflammation With Hemophagocytic Lymphohistiocytosis, Hepatosplenomegaly, Fetal Thrombotic Vasculopathy, and Congenital Anemia and Ascites

(2017) Jiancong Liang et al.   PEDIATRIC AND DEVELOPMENTAL PATHOLOGY

Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study

(2017) Veronika K. Jaeger et al.   RHEUMATOLOGY

Gasdermins: Effectors of Pyroptosis

(2017) Stephen B. Kovacs et al.   TRENDS IN CELL BIOLOGY

Identification of a High-Frequency SomaticNLRC4Mutation as a Cause of Autoinflammation by Pluripotent Cell-Based Phenotype Dissection

(2017) Yuri Kawasaki et al.   Arthritis & Rheumatology

Reduction in C-reactive protein indicates successful targeting of the IL-1/IL-6 axis resulting in improved survival in early stage multiple myeloma

(2016) John A. Lust et al.   AMERICAN JOURNAL OF HEMATOLOGY

A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD ( NLRP1- associated autoinflammation with arthritis and dyskeratosis)

(2016) Sylvie Grandemange et al.   ANNALS OF THE RHEUMATIC DISEASES

Erythematous nodes, urticarial rash and arthralgias in a large pedigree withNLRC4-related autoinflammatory disease, expansion of the phenotype

(2016) C.M.L. Volker-Touw et al.   BRITISH JOURNAL OF DERMATOLOGY

Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation

(2016) Franklin L. Zhong et al.   CELL

Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores

(2016) Xing Liu et al.   NATURE

NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux

(2016) Yuan He et al.   NATURE

Control of the innate immune response by the mevalonate pathway

(2016) Murali K Akula et al.   NATURE IMMUNOLOGY

Pyrin inflammasome activation and RhoA signaling in the autoinflammatory diseases FMF and HIDS

(2016) Yong Hwan Park et al.   NATURE IMMUNOLOGY

Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes

(2016) Torbjörn Kullenberg et al.   RHEUMATOLOGY

Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation

(2016) Seth L. Masters et al.   Science Translational Medicine

Molecular Mechanisms in Genetically Defined Autoinflammatory Diseases: Disorders of Amplified Danger Signaling

(2015) Adriana Almeida de Jesus et al.   Annual Review of Immunology

Hemophagocytic lymphohistiocytosis (HLH): A heterogeneous spectrum of cytokine-driven immune disorders

(2015) Ellen Brisse et al.   CYTOKINE & GROWTH FACTOR REVIEWS

A Genome-wide CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) Screen Identifies NEK7 as an Essential Component of NLRP3 Inflammasome Activation

(2015) Jonathan L. Schmid-Burgk et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death

(2015) Jianjin Shi et al.   NATURE

In vivo genome editing using Staphylococcus aureus Cas9

(2015) F. Ann Ran et al.   NATURE

NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component

(2015) Hexin Shi et al.   NATURE IMMUNOLOGY

A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases

(2015) Rebecca C Coll et al.   NATURE MEDICINE

Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization

(2015) L. Zhang et al.   SCIENCE

In vivo gene editing in dystrophic mouse muscle and muscle stem cells

(2015) M. Tabebordbar et al.   SCIENCE

In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy

(2015) C. E. Nelson et al.   SCIENCE

An inherited mutation inNLRC4causes autoinflammation in human and mice

(2014) Akiko Kitamura et al.   JOURNAL OF EXPERIMENTAL MEDICINE

FADD and Caspase-8 Mediate Priming and Activation of the Canonical and Noncanonical Nlrp3 Inflammasomes

(2014) P. Gurung et al.   JOURNAL OF IMMUNOLOGY

Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome

(2014) Hao Xu et al.   NATURE

CRISPR-Cas systems for editing, regulating and targeting genomes

(2014) Jeffry D Sander et al.   NATURE BIOTECHNOLOGY

Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation

(2014) Neil Romberg et al.   NATURE GENETICS

An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome

(2014) Scott W Canna et al.   NATURE GENETICS

Actin polymerization as a key innate immune effector mechanism to controlSalmonellainfection

(2014) Si Ming Man et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Microenvironmental regulation of tumor progression and metastasis

(2013) Daniela F Quail et al.   NATURE MEDICINE

The ESCRT machinery

(2012) Oliver Schmidt et al.   CURRENT BIOLOGY

C-terminal Di-arginine Motif of Cdc42 Protein Is Essential for Binding to Phosphatidylinositol 4,5-Bisphosphate-containing Membranes and Inducing Cellular Transformation

(2012) Jared L. Johnson et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance

(2011) Bolormaa Vandanmagsar et al.   NATURE MEDICINE

Influenza and Meningococcal Vaccinations Are Effective in Healthy Subjects Treated with the Interleukin-1 -Blocking Antibody Canakinumab: Results of an Open-Label, Parallel Group, Randomized, Single-Center Study

(2010) A. Chioato et al.   Clinical and Vaccine Immunology

Neutralization of IFNγ defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice

(2009) Jana Pachlopnik Schmid et al.   EMBO Molecular Medicine

Induction of a Chronic Disease State in Patients With Smoldering or Indolent Multiple Myeloma by Targeting Interleukin 1β-Induced Interleukin 6 Production and the Myeloma Proliferative Component

(2009) John A. Lust et al.   MAYO CLINIC PROCEEDINGS

Apoptosis: controlled demolition at the cellular level

(2007) Rebecca C. Taylor et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY