{"doi":"10.1016/j.celrep.2021.109142","title":"Inhibitory affinity modulation of FcγRIIA ligand binding by glycosphingolipids by inside-out signaling","abstract":"The interaction of the human FcγRIIA with immune complexes (ICs) promotes neutrophil activation and thus must be tightly controlled to avoid damage to healthy tissue. Here, we demonstrate that a fungal-derived soluble β-1,3/1,6-glucan binds to the glycosphingolipid long-chain lactosylceramide (LacCer) to reduce FcγRIIA-mediated recruitment to immobilized ICs under flow, a process requiring high-affinity FcγRIIA-immunoglobulin G (IgG) interactions. The inhibition requires Lyn phosphorylation of SHP-1 phosphatase and the FcγRIIA immunotyrosine-activating motif. β-glucan reduces the effective 2D affinity of FcγRIIA for IgG via Lyn and SHP-1 and, in vivo, inhibits FcγRIIA-mediated neutrophil recruitment to intravascular IgG deposited in the kidney glomeruli in a glycosphingolipid- and Lyn-dependent manner. In contrast, β-glucan did not affect FcγR functions that bypass FcγR affinity for IgG. In summary, we have identified a pathway for modulating the 2D affinity of FcγRIIA for ligand that relies on LacCer-Lyn-SHP-1-mediated inhibitory signaling triggered by β-glucan, a previously described activator of innate immunity.","journal":"Cell Reports","year":2021,"id":200040,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"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":777710,"name":"Michael D. Brenner","orcid":null,"position":1,"is_corresponding":false},{"id":633266,"name":"Xavier Culleré","orcid":null,"position":2,"is_corresponding":false},{"id":777711,"name":"Gurpanna Saggu","orcid":null,"position":3,"is_corresponding":false},{"id":777712,"name":"Myra L. Patchen","orcid":null,"position":4,"is_corresponding":false},{"id":777161,"name":"Nandita Bose","orcid":"0000-0002-9025-6805","position":5,"is_corresponding":false},{"id":777713,"name":"Saki Mihori","orcid":null,"position":6,"is_corresponding":false},{"id":336859,"name":"Zhou Yuan","orcid":"0000-0003-3437-0125","position":7,"is_corresponding":false},{"id":322389,"name":"Clifford A. Lowell","orcid":"0000-0002-0467-7073","position":8,"is_corresponding":false},{"id":336861,"name":"Cheng Zhu","orcid":"0000-0002-1718-565X","position":9,"is_corresponding":false},{"id":631783,"name":"Tanya N. Mayadas","orcid":"0000-0002-3604-4457","position":10,"is_corresponding":false},{"id":633267,"name":"Koshu Okubo","orcid":null,"position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-18T23:50:44.479665Z","pmid":"34010642","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":[]}