{"doi":"10.1101/2023.03.27.534340","title":"Temporal perturbation of STAT1/2 activity reveals dynamic ligand discrimination of type I interferon signaling","abstract":"SUMMARY Type-I interferon (IFN-I) subtypes signal through the same IFNα receptor (IFNAR), and initiate temporal STAT1/2 activation to orchestrate innate and adaptive immunity. It remains unknown how IFNAR discriminates between subtypes (e.g., IFNα and IFNβ), and how STAT1/2 signaling is affected by time-varying inputs. Here, we utilize our microfluidic system and live-cell imaging to quantify STAT1/2 activation dynamics in a reporter fibroblast model. Population-averaged and single-cell analyses reveal distinct STAT1/2 responses to various IFNα and IFNβ inputs. Upon continuous stimulation, cells show less sensitivity but more sustained responses to IFNα over IFNβ. A short IFNα pulse induces nearly homogeneous STAT1/2 dynamics, in contrast to heterogeneous responses in IFNβ-pulsed cells. Distinct STAT1/2 refractory states emerge upon exposure to repeated IFN-I pulses, while alternating pulse stimulation reveals that IFNβ can revoke STAT1/2 refractoriness caused by IFNα, but not vice versa. These findings highlight the differences between IFNα and IFNβ signaling and how they can elicit distinct temporal cellular behaviors during viral infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":404026,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"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":1181862,"name":"Thomas van de Kreeke","orcid":null,"position":1,"is_corresponding":false},{"id":1181499,"name":"Laura C. Van Eyndhoven","orcid":"0000-0001-7230-1134","position":2,"is_corresponding":false},{"id":862113,"name":"Jurjen Tel","orcid":"0000-0002-7213-3422","position":3,"is_corresponding":false},{"id":1181498,"name":"Haowen Yang","orcid":"0000-0002-3196-8917","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:20:40.264741Z","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":[]}