{"doi":"10.1016/j.cmet.2022.07.005","title":"CD24-Siglec axis is an innate immune checkpoint against metaflammation and metabolic disorder","abstract":"The molecular interactions that regulate chronic inflammation underlying metabolic disease remain largely unknown. Since the CD24-Siglec interaction regulates inflammatory response to danger-associated molecular patterns (DAMPs), we have generated multiple mouse strains with single or combined mutations of Cd24 or Siglec genes to explore the role of the CD24-Siglec interaction in metaflammation and metabolic disorder. Here, we report that the CD24-Siglec-E axis, but not other Siglecs, is a key suppressor of obesity-related metabolic dysfunction. Inactivation of the CD24-Siglec-E pathway exacerbates, while CD24Fc treatment alleviates, diet-induced metabolic disorders, including obesity, dyslipidemia, insulin resistance, and nonalcoholic steatohepatitis (NASH). Mechanistically, sialylation-dependent recognition of CD24 by Siglec-E induces SHP-1 recruitment and represses metaflammation to protect against metabolic syndrome. A first-in-human study of CD24Fc (NCT02650895) supports the significance of this pathway in human lipid metabolism and inflammation. These findings identify the CD24-Siglec-E axis as an innate immune checkpoint against metaflammation and metabolic disorder and suggest a promising therapeutic target for metabolic disease.","journal":"Cell Metabolism","year":2022,"id":236527,"datarank":1.7868689013661543,"base_score":4.23410650459726,"endowment":4.23410650459726,"self_citation_contribution":0.635115975689589,"citation_network_contribution":1.1517529256765653,"self_endowment_contribution":0.635115975689589,"citer_contribution":1.1517529256765653,"corpus_percentile":null,"corpus_rank":null,"citation_count":68,"citer_count":66,"citers_with_citation_signal":51,"citers_with_endowment":51,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02650895"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":857315,"name":"Mingyue Liu","orcid":"0000-0002-4334-5354","position":1,"is_corresponding":false},{"id":243097,"name":"Jifeng Zhang","orcid":"0000-0001-5161-4705","position":2,"is_corresponding":false},{"id":857316,"name":"Nicholas K. Brown","orcid":"0000-0002-0046-2315","position":3,"is_corresponding":false},{"id":280723,"name":"Peng Zhang","orcid":"0000-0002-6218-1885","position":4,"is_corresponding":false},{"id":857317,"name":"Yan Zhang","orcid":"0000-0002-9556-0240","position":5,"is_corresponding":false},{"id":640645,"name":"Heng Liu","orcid":"0000-0003-3937-4985","position":6,"is_corresponding":false},{"id":418656,"name":"Xuexiang Du","orcid":"0000-0002-7424-7343","position":7,"is_corresponding":false},{"id":311124,"name":"Wei Wu","orcid":"0000-0003-2892-5956","position":8,"is_corresponding":false},{"id":419377,"name":"Martin Devenport","orcid":null,"position":9,"is_corresponding":false},{"id":858189,"name":"W Tao","orcid":null,"position":10,"is_corresponding":false},{"id":281379,"name":"Yang Mao‐Draayer","orcid":"0000-0001-6248-3480","position":11,"is_corresponding":false},{"id":436705,"name":"Guo‐Yun Chen","orcid":null,"position":12,"is_corresponding":false},{"id":237553,"name":"Y. Eugene Chen","orcid":"0000-0003-2357-7825","position":13,"is_corresponding":false},{"id":418660,"name":"Pan Zheng","orcid":"0000-0003-2598-3544","position":14,"is_corresponding":false},{"id":857318,"name":"Yang Liu","orcid":"0000-0002-2748-4303","position":15,"is_corresponding":false},{"id":337596,"name":"Xu Wang","orcid":"0000-0001-8428-9339","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T00:22:03.686498Z","pmid":"35921817","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":[]}