{"doi":"10.1101/2023.01.30.526196","title":"TGF-β downregulates antigen processing and presentation genes and MHC I surface expression through a Smad3-dependent mechanism","abstract":"Abstract Regulation of MHC I surface expression by TGF-β is important for controlling cell-mediated immune responses, but how TGF-β downregulates MHC I is unknown. We investigated this mechanism using flow cytometry and RNA-sequencing to identify the major TGF-β signaling pathway and target genes involved. All three isoforms of TGF-β were found to have similar abilities to downregulate constitutive MHC I surface expression. Inhibiting the type I TGF-β receptor, ALK5, as well the canonical TGF-β signaling molecule Smad3, prevented TGF-β from downregulating MHC I surface expression. RNA-sequencing from horse and human mesenchymal stem cells revealed that multiple genes associated with antigen processing and presentation were downregulated in TGF-β-treated cells with B2M and ERAP1 being downregulated in both species. While downregulation of MHC I surface expression a slow process that continued past 24 hours after TGF-β treatment, downregulation of gene expression of ERAP1 occurred within 12 hours after treatment. B2M expression was not consistently downregulated until after 24 hours and TAP2 expression was inconsistent over a 72-hour period, although it was significantly downregulated at 12 hours after TGF-β treatment. This data supports that TGF-β downregulates antigen processing and presentation genes resulting in decreased surface expression of MHC I through a Smad3-dependent mechanism.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":391208,"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":0.9583,"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":1163961,"name":"Anna L. Hinson","orcid":null,"position":1,"is_corresponding":false},{"id":228261,"name":"Lauren V. Schnabel","orcid":"0000-0002-1993-8141","position":2,"is_corresponding":false},{"id":725967,"name":"Alix K. Berglund","orcid":"0000-0001-8913-7924","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:18:42.653719Z","pmid":null,"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":[]}