{"doi":"10.1126/sciimmunol.adr0517","title":"TRAF3 is critical for initial T follicular helper cell specification via coordination of the IL-6R/IL-2R–BCL6 signaling nexus","abstract":"CD4 + T follicular helper (T FH ) cells are essential for orchestrating robust humoral immunity, yet the signals that initiate T FH cell differentiation are not fully understood. We identified that the adapter protein TRAF3 was required for T FH cell differentiation and function during systemic inflammatory infections. Loss of CD4 + T cell–intrinsic TRAF3 impaired chromatin remodeling and transcriptional programming essential for T FH cell initiation and instead augmented T H 1 development and function. TRAF3-deficient CD4 + T cells exhibited altered interleukin-6 (IL-6) and IL-2 responsiveness, which were coupled to failures in BCL6 expression. Enforced expression of either IL-6 receptor or BCL6 or blockade of IL-2 signaling was sufficient to rescue T FH cell differentiation. Human CD4 + T cells lacking TRAF3 exhibited impaired T FH polarization, supporting a conserved mechanism by which TRAF3 regulates CD4 + T cell fate determination. Thus, TRAF3 functions at the nexus of cytokine, transcriptional, and epigenetic nodes that promote the T FH cell specification during infection.","journal":"Science Immunology","year":2025,"id":543117,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9473,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"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":1432847,"name":"Regina Antonetti","orcid":null,"position":1,"is_corresponding":false},{"id":372341,"name":"Tina Arkee","orcid":"0000-0003-4983-8958","position":2,"is_corresponding":false},{"id":971169,"name":"Emma E. Hornick","orcid":"0000-0002-1355-0576","position":3,"is_corresponding":false},{"id":271042,"name":"Hai‐Hui Xue","orcid":"0000-0002-9163-7669","position":4,"is_corresponding":false},{"id":372345,"name":"Gail A. Bishop","orcid":"0000-0002-1291-5078","position":5,"is_corresponding":false},{"id":271045,"name":"Noah S. Butler","orcid":"0000-0002-1429-0796","position":6,"is_corresponding":false},{"id":490433,"name":"Peng Shao","orcid":"0000-0002-8453-6480","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:53:00.171379Z","pmid":"39951546","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":[]}