{"doi":"10.1016/j.celrep.2023.113581","title":"The tetrapeptide sequence of IL-18 and IL-1β regulates their recruitment and activation by inflammatory caspases","abstract":"Inflammasomes are multiprotein signaling complexes that activate the innate immune system. Canonical inflammasomes recruit and activate caspase-1, which then cleaves and activates IL-1β and IL-18, as well as gasdermin D (GSDMD) to induce pyroptosis. In contrast, non-canonical inflammasomes, caspases-4/-5 (CASP4/5) in humans and caspase-11 (CASP11) in mice, are known to cleave GSDMD, but their role in direct processing of other substrates besides GSDMD has remained unknown. Here, we show that CASP4/5 but not CASP11 can directly cleave and activate IL-18. However, CASP4/5/11 can all cleave IL-1β to generate a 27-kDa fragment that deactivates IL-1β signaling. Mechanistically, we demonstrate that the sequence identity of the tetrapeptide sequence adjacent to the caspase cleavage site regulates IL-18 and IL-1β recruitment and activation. Altogether, we have identified new substrates of the non-canonical inflammasomes and reveal key mechanistic details regulating inflammation that may aid in developing new therapeutics for immune-related disorders.","journal":"Cell Reports","year":2023,"id":318459,"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":65,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":865491,"name":"Claudia Hernandez-Chavez","orcid":null,"position":1,"is_corresponding":false},{"id":646216,"name":"Christopher M. Bourne","orcid":"0000-0001-9290-4223","position":2,"is_corresponding":false},{"id":672558,"name":"Rachel Richards","orcid":"0000-0002-4872-0037","position":3,"is_corresponding":false},{"id":1025725,"name":"Mark B. Bray","orcid":"0000-0003-2500-9549","position":4,"is_corresponding":false},{"id":1025726,"name":"Jan L. Lopez","orcid":"0009-0008-6245-2471","position":5,"is_corresponding":false},{"id":470229,"name":"Tamanna Srivastava","orcid":"0009-0002-9025-1542","position":6,"is_corresponding":false},{"id":854642,"name":"Marisa S. Egan","orcid":"0000-0001-6191-5552","position":7,"is_corresponding":false},{"id":1025727,"name":"Jenna Zhang","orcid":"0000-0001-7016-7947","position":8,"is_corresponding":false},{"id":1026284,"name":"William Yoo","orcid":null,"position":9,"is_corresponding":false},{"id":299108,"name":"Sunny Shin","orcid":"0000-0001-5214-9577","position":10,"is_corresponding":false},{"id":1026285,"name":"Bohdana M. Discher","orcid":null,"position":11,"is_corresponding":false},{"id":260796,"name":"Cornelius Y. Taabazuing","orcid":"0000-0003-2361-5457","position":12,"is_corresponding":false},{"id":1025724,"name":"Patrick M. Exconde","orcid":"0009-0001-7299-8274","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T01:07:01.300821Z","pmid":"38103201","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":[]}