TRIM21 facilitates inflammasome assembly and contributes to autoinflammatory disease
Year: 2026
Type: article
Abstract: Inflammasomes are cytosolic multiprotein complexes facilitating the maturation and release of the inflammatory cytokines interleukin (IL)-1β and IL-18 and pyroptosis. ASC (apoptosis-associated-speck-like protein containing a CARD) is the central inflammasome adaptor. ASC polymerization is crucial for inflammasome assembly, and ASC particle release propagates inflammasome responses to bystander cells. However, control of inflammasome and ASC particle assembly to limit chronic inflammation and the emergence of autoinflammatory diseases is still incompletely understood. Here, we show that the E3 ubiquitin ligase TRIM (tripartite-motif-containing protein) 21, a common autoantigen in autoimmune diseases, is involved in inflammasome assembly. Specifically, TRIM21 binds to and ubiquitinates ASC to facilitate ASC/NLRP3 interactions, ASC polymerization and the release of ASC/TRIM21-containing particles during pyroptosis in human and mouse macrophages. Furthermore, we detect systemic ASC/TRIM21 particles and autoantibodies in human and mouse autoinflammatory disease. Thus, our findings highlight a previously unrecognized role of TRIM21 as an inflammasome component and driver of autoinflammation.
Source: Nature Communications
Authors: Jessica Carriere, Chawon Yun, Sonal Khare, Sana Ismaeel, Elisabeth Jäger, Vinicius Dantas Martins, Kaiden A. Sims, Lan H. Chu, Huyen Nguyen, Lucia de Almeida, Janset Onyuru, Justin Ruiz, Hemisha Khatri, Savita Devi, Jae Jin Chae, Daniel L. Kastner, Lori Broderick, Hal M. Hoffman, Andrea Dorfleutner, Christian Stehlik
Institutions: Cedars-Sinai Medical Center, Northwestern University, Korea University, University of Washington, Lurie Children's Hospital, University of California San Diego, Rady Children's Hospital-San Diego, University of Miami, Arrowhead Pharmaceuticals (United States), Indian Institute of Technology Hyderabad, National Institutes of Health, National Human Genome Research Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: Role of a caspase-1 inhibitory protein in cardiovascular disease, Uncovering the role of extracellular ASC danger particles in atherosclerosis and gout, G311672864, NLRP11 shapes macrophage metabolism and inflammasome activation in response to atherogenic lipids, G4495638443, G5049474463, G532878718, Role of POP2 in metabolic reprogramming, macrophage activation and inflammation associated with atherosclerosis., A novel role of the Angiotensin-Converting Enzyme in the hyper-inflammatory response, Role of the novel inflammasome component TRIM21 in atherosclerosis., The pyrin domain-only protein POP3 ameliorates colon cancer via type I interferon signaling, CARD-only protein regulation of cytosolic Pattern Recognition Receptor signaling, A novel mechanism for NLRP3 inflammasome activation in human macrophages, POP3 regulates type I interferon and ameliorates intestinal inflammation
OpenAlex ID: W7162093136