{"doi":"10.3389/fimmu.2024.1523306","title":"Connexin 43 and Pannexin 1 hemichannels as endogenous regulators of innate immunity in sepsis","abstract":"Sepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infections that is initiated by the body’s innate immune system. Nearly a decade ago, we discovered that bacterial lipopolysaccharide (LPS) and serum amyloid A (SAA) upregulated Connexin 43 (Cx43) and Pannexin 1 (Panx1) hemichannels in macrophages. When overexpressed, these hemichannels contribute to sepsis pathogenesis by promoting ATP efflux, which intensifies the double-stranded RNA-activated protein kinase R (PKR)-dependent inflammasome activation, pyroptosis, and the release of pathogenic damage-associated molecular pattern (DAMP) molecules, such as HMGB1. Mimetic peptides targeting specific regions of Cx43 and Panx1 can distinctly modulate hemichannel activity in vitro , and diversely impact sepsis-induced lethality in vivo . Along with extensive supporting evidence from others, we now propose that hemichannel molecules play critical roles as endogenous regulators of innate immunity in sepsis.","journal":"Frontiers in Immunology","year":2024,"id":446198,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1263525,"name":"Lou Li","orcid":null,"position":1,"is_corresponding":false},{"id":1047447,"name":"Weiqiang Chen","orcid":"0000-0002-3592-2318","position":2,"is_corresponding":false},{"id":565052,"name":"Xiaoling Qiang","orcid":"0000-0001-9176-7407","position":3,"is_corresponding":false},{"id":565053,"name":"Shu Zhu","orcid":"0000-0003-2211-9646","position":4,"is_corresponding":false},{"id":109941,"name":"Haichao Wang","orcid":"0000-0002-0211-9000","position":5,"is_corresponding":false},{"id":516696,"name":"Jianhua Li","orcid":"0000-0001-5123-485X","position":0,"is_corresponding":true}],"reference_count":148,"raw_metadata":null,"created_at":"2026-07-19T02:01:50.465308Z","pmid":"39763679","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":[]}