{"doi":"10.3389/fimmu.2022.935394","title":"IL-6-Driven pSTAT1 Response Is Linked to T Cell Features Implicated in Early Immune Dysregulation","abstract":"Elevated levels and enhanced sensing of the pro-inflammatory cytokine interleukin-6 (IL-6) are key features of many autoimmune and inflammatory diseases. To better understand how IL-6 signaling may influence human T cell fate, we investigated the relationships between levels of components of the IL-6R complex, pSTAT responses, and transcriptomic and translational changes in CD4 + and CD8 + T cell subsets from healthy individuals after exposure to IL-6. Our findings highlight the striking heterogeneity in mbIL-6R and gp130 expression and IL-6-driven pSTAT1/3 responses across T cell subsets. Increased mbIL-6R expression correlated with enhanced signaling via pSTAT1 with less impact on pSTAT3, most strikingly in CD4 + naïve T cells. Additionally, IL-6 rapidly induced expression of transcription factors and surface receptors expressed by T follicular helper cells and altered expression of markers of apoptosis. Importantly, many of the features associated with the level of mbIL-6R expression on T cells were recapitulated both in the setting of tocilizumab therapy and when comparing donor CD4 + T cells harboring the genetic variant, IL6R Asp358Ala (rs2228145), known to alter mbIL-6R expression on T cells. Collectively, these findings should be taken into account as we consider the role of IL-6 in disease pathogenesis and translating IL-6 biology into effective therapies for T cell-mediated autoimmune disease.","journal":"Frontiers in Immunology","year":2022,"id":267166,"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":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":308285,"name":"Kirsten E. Diggins","orcid":"0000-0003-1622-0158","position":1,"is_corresponding":false},{"id":885732,"name":"Britta E. Jones","orcid":"0000-0001-5687-1807","position":2,"is_corresponding":false},{"id":902030,"name":"Christian Hundhausen","orcid":"0000-0002-6905-6753","position":3,"is_corresponding":false},{"id":885733,"name":"Megan D. Maerz","orcid":"0000-0003-1798-7510","position":4,"is_corresponding":false},{"id":670780,"name":"Anne M. Hocking","orcid":"0000-0003-2130-3732","position":5,"is_corresponding":false},{"id":333914,"name":"Srinath Sanda","orcid":"0000-0002-6983-6864","position":6,"is_corresponding":false},{"id":71415,"name":"Carla J. Greenbaum","orcid":"0000-0003-4451-9800","position":7,"is_corresponding":false},{"id":308290,"name":"Peter S. Linsley","orcid":"0000-0002-8960-4307","position":8,"is_corresponding":false},{"id":644646,"name":"Karen Cerosaletti","orcid":"0000-0002-7403-6239","position":9,"is_corresponding":false},{"id":226226,"name":"Jane H. Buckner","orcid":"0000-0002-9005-1885","position":10,"is_corresponding":false},{"id":539627,"name":"Katharina Lambert","orcid":"0000-0002-1998-0024","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T00:27:02.050512Z","pmid":"35911690","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":[]}