{"doi":"10.1016/j.celrep.2024.114072","title":"Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance","abstract":"Medullary thymic epithelial cells (mTECs) are essential for the establishment of self-tolerance in T cells. Promiscuous gene expression by a subpopulation of mTECs regulated by the nuclear protein Aire contributes to the display of self-genomic products to newly generated T cells. Recent reports have highlighted additional self-antigen-displaying mTEC subpopulations, namely Fezf2-expressing mTECs and a mosaic of self-mimetic mTECs including thymic tuft cells. In addition, a functionally different subset of mTECs produces chemokine CCL21, which attracts developing thymocytes to the medullary region. Here, we report that CCL21 + mTECs and Aire + mTECs non-redundantly cooperate to direct self-tolerance to prevent autoimmune pathology by optimizing the deletion of self-reactive T cells and the generation of regulatory T cells. We also detect cooperation for self-tolerance between Aire and Fezf2, the latter of which unexpectedly regulates thymic tuft cells. Our results indicate an indispensable interplay among functionally diverse mTECs for the establishment of central self-tolerance.","journal":"Cell Reports","year":2024,"id":424995,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":759350,"name":"Mami Matsuda‐Lennikov","orcid":"0000-0001-9845-2205","position":1,"is_corresponding":false},{"id":1222584,"name":"Felix Kalle-Youngoue","orcid":null,"position":2,"is_corresponding":false},{"id":1222585,"name":"Akihide Shimizu","orcid":null,"position":3,"is_corresponding":false},{"id":425135,"name":"Abdalla Abdelmaksoud","orcid":null,"position":4,"is_corresponding":false},{"id":226280,"name":"Michael C. Kelly","orcid":"0000-0003-0654-2778","position":5,"is_corresponding":false},{"id":695447,"name":"Naozumi Ishimaru","orcid":"0000-0003-1087-8338","position":6,"is_corresponding":false},{"id":314995,"name":"Yousuke Takahama","orcid":"0000-0002-4992-9174","position":7,"is_corresponding":false},{"id":695445,"name":"Ushio Aya","orcid":"0000-0002-0950-5545","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T01:58:21.523756Z","pmid":"38581680","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":[]}