{"doi":"10.1073/pnas.2323052121","title":"Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis","abstract":"Cardiac myosin-specific (MyHC) T cells drive the disease pathogenesis of immune checkpoint inhibitor–associated myocarditis (ICI-myocarditis). To determine whether MyHC T cells are tissue-resident memory T (T RM ) cells, we characterized cardiac T RM cells in naive mice and established that they have a distinct phenotypic and transcriptional profile that can be defined by their upregulation of CD69, PD-1, and CXCR6. We then investigated the effects of cardiac injury through a modified experimental autoimmune myocarditis mouse model and an ischemia–reperfusion injury mouse model and determined that cardiac inflammation induces the recruitment of autoreactive MyHC T RM cells, which coexpress PD-1 and CD69. To investigate whether the recruited MyHC T RM cells could increase susceptibility to ICI-myocarditis, we developed a two-hit ICI-myocarditis mouse model where cardiac injury was induced, mice were allowed to recover, and then were treated with anti-PD-1 antibodies. We determined that mice who recover from cardiac injury are more susceptible to ICI-myocarditis development. We found that murine and human T RM cells share a similar location in the heart and aggregate along the perimyocardium. We phenotyped cells obtained from pericardial fluid from patients diagnosed with dilated cardiomyopathy and ischemic cardiomyopathy and established that pericardial T cells are predominantly CD69 + T RM cells that up-regulate PD-1. Finally, we determined that human pericardial macrophages produce IL-15, which supports and maintains pericardial T RM cells.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":421712,"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":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"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":1081639,"name":"Abdel Daoud","orcid":"0009-0004-6661-5670","position":1,"is_corresponding":false},{"id":1214646,"name":"Vitali Rusinkevich","orcid":"0000-0002-7215-1452","position":2,"is_corresponding":false},{"id":465560,"name":"Ivana Jurčová","orcid":"0000-0002-0872-4877","position":3,"is_corresponding":false},{"id":465559,"name":"Monica V. Talor","orcid":"0000-0002-8275-5698","position":4,"is_corresponding":false},{"id":1082615,"name":"Robin A. Welsh","orcid":"0000-0001-5822-0485","position":5,"is_corresponding":false},{"id":848045,"name":"David M. Hughes","orcid":"0000-0002-1287-9994","position":6,"is_corresponding":false},{"id":1215219,"name":"Kateřina Zemanová","orcid":null,"position":7,"is_corresponding":false},{"id":465561,"name":"Ilja Střı́ž","orcid":"0000-0001-9269-5652","position":8,"is_corresponding":false},{"id":278995,"name":"Jody E. Hooper","orcid":"0000-0002-8209-3559","position":9,"is_corresponding":false},{"id":340036,"name":"Josef Kautzner","orcid":"0000-0002-1632-6182","position":10,"is_corresponding":false},{"id":748802,"name":"Petr Peichl","orcid":"0000-0002-5625-0071","position":11,"is_corresponding":false},{"id":465562,"name":"Vojtěch Melenovský","orcid":"0000-0001-8921-7078","position":12,"is_corresponding":false},{"id":465557,"name":"Taejoon Won","orcid":"0000-0001-5968-2016","position":13,"is_corresponding":false},{"id":465563,"name":"Daniela Čiháková","orcid":"0000-0002-8713-2860","position":14,"is_corresponding":false},{"id":1116423,"name":"Hannah Kalinoski","orcid":"0000-0002-2732-0077","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T01:57:41.370244Z","pmid":"39378095","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":[]}