{"doi":"10.3390/ijms26178377","title":"T Cell Activation Induces Synthesis of CD47 Proteoglycan Isoforms and Their Release in Extracellular Vesicles","abstract":"Thrombospondin-1 potently inhibits T cell activation by engaging its cell surface receptor CD47. This inhibitory signal requires glycosaminoglycan modification of CD47. CD47 also regulates the composition of RNAs in extracellular vesicles released by T cells and their functional activities. Because CD47 is also present in extracellular vesicles, we examined the effect of T cell activation on CD47 glycoforms in T cells and extracellular vesicles released by these cells. Activation increased both heparan and chondroitin sulfate biosynthesis by globally inducing mRNA levels of the respective glycosaminoglycan synthases and sulfotransferases. T cell activation in the presence of thrombospondin-1 inhibited induction of these biosynthetic enzymes, but not in cells lacking CD47. Therefore, CD47 signaling controls its own post-translational modification by glycosaminoglycans that are required for thrombospondin-1 signaling. Activation of Jurkat T lymphoblasts and primary CD4 and CD8 T cells increased the release of proteoglycan isoforms of CD47 and amyloid precursor-like protein-2 associated with extracellular vesicles and smaller macromolecular complexes. However, cell surface levels of CD47 were minimally changed during activation. BJAB and RAJI B cell lines also produced CD47+ extracellular vesicles and showed increased release of highly glycosylated CD47 following B cell receptor engagement. Therefore, T and B lymphocyte activation results in a selective increase in the synthesis and release of extracellular vesicles containing proteoglycan isoforms of CD47.","journal":"International Journal of Molecular Sciences","year":2025,"id":554006,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1450867,"name":"Светлана А. Кузнецова","orcid":"0000-0002-2789-5890","position":1,"is_corresponding":false},{"id":1451342,"name":"John M. Sipes","orcid":null,"position":2,"is_corresponding":false},{"id":707703,"name":"Satya P. Singh","orcid":"0000-0003-3159-3622","position":3,"is_corresponding":false},{"id":706567,"name":"Rafael Villasmil","orcid":"0000-0002-8956-2979","position":4,"is_corresponding":false},{"id":318082,"name":"David D. Roberts","orcid":"0000-0002-2481-2981","position":5,"is_corresponding":false},{"id":322438,"name":"Sukhbir Kaur","orcid":"0000-0003-0513-6225","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T02:54:45.872391Z","pmid":"40943300","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":[]}