CARD-only proteins regulate in vivo inflammasome responses and ameliorate gout

Savita Devi; Mohanalaxmi Indramohan; Elisabeth Jäger; Jessica Carriere; Lan H. Chu; Lucia de Almeida; David R. Greaves; Christian Stehlik; Andrea Dorfleutner

Cell Reports (Mar 2023)

CARD-only proteins regulate in vivo inflammasome responses and ameliorate gout

Savita Devi,
Mohanalaxmi Indramohan,
Elisabeth Jäger,
Jessica Carriere,
Lan H. Chu,
Lucia de Almeida,
David R. Greaves,
Christian Stehlik,
Andrea Dorfleutner

Affiliations

Savita Devi: Department of Academic Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
Mohanalaxmi Indramohan: Department of Academic Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
Elisabeth Jäger: Department of Academic Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
Jessica Carriere: Department of Academic Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
Lan H. Chu: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Driskill Graduate Program in Life Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Lucia de Almeida: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
David R. Greaves: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
Christian Stehlik: Department of Academic Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; The Kao Autoimmunity Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; Corresponding author
Andrea Dorfleutner: Department of Academic Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; The Kao Autoimmunity Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 3
p. 112265

Abstract

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Summary: Inflammatory responses are crucial for controlling infections and initiating tissue repair. However, excessive and uncontrolled inflammation causes inflammatory disease. Processing and release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 depend on caspase-1 activation within inflammasomes. Assembly of inflammasomes is initiated upon activation of cytosolic pattern recognition receptors (PRRs), followed by sequential polymerization of pyrin domain (PYD)-containing and caspase recruitment domain (CARD)-containing proteins mediated by homotypic PYD and CARD interactions. Small PYD- or CARD-only proteins (POPs and COPs, respectively) evolved in higher primates to target these crucial interactions to limit inflammation. Here, we show the ability of COPs to regulate inflammasome activation by modulating homotypic CARD-CARD interactions in vitro and in vivo. CARD16, CARD17, and CARD18 displace crucial CARD interactions between caspase-1 proteins through competitive binding and ameliorate uric acid crystal-mediated NLRP3 inflammasome activation and inflammatory disease. COPs therefore represent an important family of inflammasome regulators and ameliorate inflammatory disease.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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