{"doi":"10.1016/j.celrep.2025.115798","title":"Single-cell analysis of temporal immune cell dynamics in alopecia areata reveals a causal role for clonally expanded CD8+ T cells in disease","abstract":"Alopecia areata (AA) is an immune-mediated hair loss disorder characterized by the infiltration of immune cells, including clonally expanded CD8 + T cells into lesional skin. To explore the link between CD8 + T cell clonality and disease pathogenicity, we conducted single-cell RNA and T cell receptor (TCR) sequencing in the C3H/HeJ mouse model of AA. We analyzed T cells derived from skin and skin-draining lymph nodes to capture both the end-organ and the site of antigen priming and found striking hyper-expansion of T cell clones associated with disease onset. Using the hyperexpanded CD8 + TCR sequences, we generated TCR retrogenic mice engineered to express a single clonotypic T cell population, applied CRISPR-Cas9 to engineer these TCR sequences within CD8 + T cells, and performed depletion experiments to demonstrate that expanded CD8 + T cell clones are sufficient to initiate disease, establishing a causal relationship between CD8 + T cell clonality and pathogenicity in disease.","journal":"Cell Reports","year":2025,"id":513889,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"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":641049,"name":"Yuqian Chang","orcid":"0000-0002-8930-6860","position":1,"is_corresponding":false},{"id":502490,"name":"Eunice Lee","orcid":"0000-0002-4900-0955","position":2,"is_corresponding":false},{"id":1376379,"name":"Valia P Leifer","orcid":null,"position":3,"is_corresponding":false},{"id":346991,"name":"Eddy Hsi Chun Wang","orcid":"0000-0001-7785-1442","position":4,"is_corresponding":false},{"id":783953,"name":"Rolando Pérez‐Lorenzo","orcid":"0000-0002-9355-9617","position":5,"is_corresponding":false},{"id":345701,"name":"Annemieke de Jong","orcid":"0000-0001-6707-6585","position":6,"is_corresponding":false},{"id":346992,"name":"Angela M. Christiano","orcid":"0000-0002-6071-9784","position":7,"is_corresponding":false},{"id":641048,"name":"Zhenpeng Dai","orcid":"0000-0002-3679-6675","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:48:23.284782Z","pmid":"40531623","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":[]}