{"doi":"10.1161/circresaha.121.319153","title":"NLRP3 Inflammasome Mediates Immune-Stromal Interactions in Vasculitis","abstract":"Rationale: NLRP3 (NLR family pyrin domain containing 3) activation and IL-1β (interleukin-1β) production are implicated in Kawasaki disease (KD) pathogenesis; however, a detailed and complete characterization of the molecular networks and cellular subsets involved in the development of cardiovascular lesions is still lacking. Objective: Here, in a murine model of KD vasculitis, we used single-cell RNA sequencing and spatial transcriptomics to determine the cellular landscape of inflamed vascular tissues. Methods and Results: We observe infiltrations of innate and adaptive immune cells in murine KD cardiovascular lesions, associated with increased expression of Nlrp3 and Il1b . Monocytes, macrophages, and dendritic cells were the main sources of IL-1β, whereas fibroblasts and vascular smooth muscle cells (VSMCs) expressed high levels of IL-1 receptor. VSMCs type 1 surrounding the inflamed coronary artery undergo a phenotype switch to become VSMCs type 2, which are characterized by gene expression changes associated with decreased contraction and enhanced migration and proliferation. Genetic inhibition of IL-1β signaling on VSMCs efficiently attenuated the VSMCs type 2 phenotypic switch and the development of cardiovascular lesions during murine KD vasculitis. In addition, pharmacological inhibition of NLRP3 prevented the development of cardiovascular inflammation. Conclusions: Our studies unravel the cellular diversity involved in IL-1β production and signaling in murine KD cardiovascular lesions and provide the rationale for therapeutic strategies targeting NLRP3 to inhibit cardiovascular lesions associated with KD.","journal":"Circulation Research","year":2021,"id":152341,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":76,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":21637,"name":"David Zemmour","orcid":"0000-0002-0990-217X","position":1,"is_corresponding":false},{"id":640244,"name":"Masanori Abe","orcid":"0000-0002-5641-4996","position":2,"is_corresponding":false},{"id":640243,"name":"Youngho Lee","orcid":"0000-0002-5227-683X","position":3,"is_corresponding":false},{"id":646776,"name":"Meena Narayanan","orcid":"0000-0002-1807-4118","position":4,"is_corresponding":false},{"id":646777,"name":"Thacyana T. Carvalho","orcid":"0000-0002-8580-6200","position":5,"is_corresponding":false},{"id":612650,"name":"Angela C. Gomez","orcid":"0000-0001-7019-9607","position":6,"is_corresponding":false},{"id":647381,"name":"Daisy Martinon","orcid":null,"position":7,"is_corresponding":false},{"id":555558,"name":"Chintda Santiskulvong","orcid":"0000-0002-4762-991X","position":8,"is_corresponding":false},{"id":390154,"name":"Michael C. Fishbein","orcid":"0000-0002-6591-6306","position":9,"is_corresponding":false},{"id":33509,"name":"Shuang Chen","orcid":"0000-0002-2919-4967","position":10,"is_corresponding":false},{"id":315014,"name":"Timothy R. Crother","orcid":"0000-0001-8465-6127","position":11,"is_corresponding":false},{"id":315013,"name":"Kenichi Shimada","orcid":"0000-0001-8213-5686","position":12,"is_corresponding":false},{"id":231575,"name":"Moshe Arditi","orcid":"0000-0001-9042-2909","position":13,"is_corresponding":false},{"id":231571,"name":"Magali Noval Rivas","orcid":"0000-0001-5570-8928","position":14,"is_corresponding":false},{"id":231570,"name":"Rebecca A. Porritt","orcid":"0000-0002-0973-5092","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:43:22.562252Z","pmid":"34517723","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}