{"doi":"10.7554/elife.107096","title":"Epidermal resident memory T cell fitness requires antigen encounter in the skin","abstract":"CD8 + tissue-resident memory T cells (T RM ) develop from effectors that seed peripheral tissues where they persist providing defense against subsequent challenges. T RM persistence requires autocrine TGFβ transactivated by integrins expressed on keratinocytes. T RM precursors that encounter antigen in the epidermis during development outcompete bystander T RM for TGFβ resulting in enhanced persistence. ScRNA-seq analysis of epidermal T RM revealed that local antigen experience in the skin resulted in an enhanced differentiation signature in comparison with bystanders. Upon recall, T RM displayed greater proliferation dictated by affinity of antigen experienced during epidermal development. Finally, local antigen experienced T RM differentially expressed TGFβRIII, which increases avidity of the TGFβRI/II receptor complex for TGFβ. Selective ablation of Tgfbr3 reduced local antigen experienced T RM capacity to persist, rendering them phenotypically like bystander T RM . Thus, antigen-driven TCR signaling in the epidermis during T RM differentiation results in a lower TGFβ requirement for persistence and increased proliferative capacity that together enhance epidermal T RM fitness.","journal":"eLife","year":2025,"id":558384,"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":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9421,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE283941","GSE297097"]},"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":271255,"name":"Toshiro Hirai","orcid":"0000-0002-9212-1664","position":1,"is_corresponding":false},{"id":271257,"name":"Haiyue Li","orcid":"0000-0001-9901-3714","position":2,"is_corresponding":false},{"id":1035571,"name":"Andrew W. Liu","orcid":"0000-0003-2355-5888","position":3,"is_corresponding":false},{"id":204878,"name":"Shannon Baker","orcid":null,"position":4,"is_corresponding":false},{"id":1169900,"name":"Ian Magill","orcid":"0009-0009-1280-3365","position":5,"is_corresponding":false},{"id":250922,"name":"Jacob E. Gillis","orcid":"0000-0001-6248-693X","position":6,"is_corresponding":false},{"id":1458818,"name":"Y. Zhang","orcid":"0009-0001-2327-0623","position":7,"is_corresponding":false},{"id":1361422,"name":"Torben Ramcke","orcid":"0000-0001-5616-845X","position":8,"is_corresponding":false},{"id":1228365,"name":"Kazuo Kurihara","orcid":"0000-0003-4964-1549","position":9,"is_corresponding":false},{"id":252445,"name":"David Masopust","orcid":"0000-0002-9440-3884","position":10,"is_corresponding":false},{"id":18942,"name":"Niroshana Anandasabapathy","orcid":"0000-0002-0473-8358","position":11,"is_corresponding":false},{"id":24597,"name":"Harinder Singh","orcid":"0000-0002-6330-8526","position":12,"is_corresponding":false},{"id":21637,"name":"David Zemmour","orcid":"0000-0002-0990-217X","position":13,"is_corresponding":false},{"id":883340,"name":"Laura K. Mackay","orcid":"0000-0002-8496-6632","position":14,"is_corresponding":false},{"id":271263,"name":"Daniel H. Kaplan","orcid":"0000-0003-0598-0047","position":15,"is_corresponding":false},{"id":1458817,"name":"E. H. Weiss","orcid":"0000-0003-2352-0036","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:55:25.969263Z","pmid":"41468295","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":[]}