{"doi":"10.1111/imr.70038","title":"Thymic Interferons: A Little Goes a Long Way","abstract":"Central tolerance is an essential process that protects the mammalian immune system from developing autoimmune reactions by forming a self-tolerant repertoire of T cells. The extent of central tolerance depends on the diversity of self-peptide-major histocompatibility complexes that thymocytes encounter on thymic antigen-presenting cells (APCs). Decades of research have demonstrated that medullary thymic epithelial cells (mTECs), a unique type of APC of stromal origin, possess an extraordinary capacity to produce and present thousands of self-peptides to developing thymocytes. This ability is facilitated by various unconventional mechanisms, including AIRE-regulated promiscuous gene expression, mimicry of peripheral cell types, and cooperative antigen transfer between different thymic APCs. Recently, several studies have reported that mTECs and other thymus-resident cells also produce tonic inflammatory signaling, which shapes the thymic microenvironment and expands the repertoire of presented inflammation-associated self-antigens (ISA). In this review, we focus on thymic interferons (IFNs), pro-inflammatory molecules produced as self-antigens by mTECs. Beyond their role as rare self-antigens critical for tolerance induction, IFNs influence the thymic microenvironment by promoting sterile inflammation, regulating the maturation of thymic APCs, and shaping T cell selection. We will discuss the production and regulation of thymic IFNs and their role in APC maturation and T cell selection.","journal":"Immunological Reviews","year":2025,"id":519635,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"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":235914,"name":"Kristin A. Hogquist","orcid":"0000-0001-9963-5687","position":1,"is_corresponding":false},{"id":864289,"name":"Matouš Vobořil","orcid":"0000-0002-3672-7629","position":0,"is_corresponding":true}],"reference_count":114,"raw_metadata":null,"created_at":"2026-07-19T02:49:18.751199Z","pmid":"40439345","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":[]}