{"doi":"10.7150/ijbs.124098","title":"Impact of rare JAK/STAT germline mutations on vaccination-induced innate immune responses in a Tyrolian population","abstract":"Vaccination triggers the release of pro-inflammatory cytokines, the stimulation of the Janus Kinase (JAK) -Signal Transducer and Activator of Transcription (STAT) pathway and the activation of interferon response genes.While some JAK/STAT variants are associated with hematopoietic malignancies, the impact of the vast majority is unknown.Here we identify JAK/STAT germline variants in a Tyrolian cohort, including octogenarians, and link specific rare variants to enhanced vaccine-induced interferon transcriptomic responses.AlphaFold 3 predicted conformational changes in JAK and STATs variants, impacting their interactions and formation of receptor complexes.We also identified co-occurring variants in TYK2 and other modulators of interferon signaling that possibly modify the impact of JAK and STAT variants in the innate immune response.Our results demonstrate that the vaccine-induced innate immune transcriptomic response can be used for an in vivo functional assessment of mutations controlling key genetic pathways in the innate immune response.","journal":"International Journal of Biological Sciences","year":2025,"id":542611,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"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":1419064,"name":"Gyuhyeok Cho","orcid":"0000-0001-6785-616X","position":1,"is_corresponding":false},{"id":1331966,"name":"Sung‐Gwon Lee","orcid":"0000-0002-0928-9950","position":2,"is_corresponding":false},{"id":1432160,"name":"Yasmin Caf","orcid":null,"position":3,"is_corresponding":false},{"id":1415926,"name":"Jungwook Kim","orcid":"0000-0001-5213-9299","position":4,"is_corresponding":false},{"id":576165,"name":"Ludwig Knabl","orcid":"0000-0001-8280-8991","position":5,"is_corresponding":false},{"id":576168,"name":"Priscilla A. Furth","orcid":"0000-0003-3883-0715","position":6,"is_corresponding":false},{"id":279569,"name":"Hye‐Kyung Lee","orcid":"0000-0002-7785-5942","position":7,"is_corresponding":false},{"id":14888,"name":"Lothar Hennighausen","orcid":"0000-0001-8319-9841","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:52:55.809501Z","pmid":"41522351","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":[]}