{"doi":"10.1101/2025.01.13.632166","title":"Damage signals preferentially activate killer CD8 <sup>+/-</sup> regulatory T cells to protect injured tissue","abstract":"SUMMARY Self-antigens that are obscure to immune cells under homeostasis, are exposed following tissue damage and can trigger autoimmunity. Our previous work showed that conventional type 1 dendritic cells (cDC1s) mediate immunoregulation after traumatic skeletal muscle injury. Here, we found that, immune responses to injury in cDC1-depleted mice ( Batf3 -/- ) mirror those of autoimmune mice ( Aire -/- ). Mechanistically, we determined that cDC1s prime killer regulatory T cells (CD8 +/- Ly49 + Tregs) which express Ly49 inhibitory receptors and HELIOS. These killer-like Tregs are clonally diverse and carry T cell receptors associated with self-reactivity and response to hydrophobicity. cDC1 or CD8 deletion promoted CD62L + CCR7 + naïve T cell retention and B cell recruitment to injured muscle. These naïve T cells, which are implicated in autoimmunity, strongly correlate with B cell abundance in the muscle and are selectively pruned by CD8 +/- Ly49 + Tregs. Furthermore, clinically used materials that promote wound healing enrich CD8 +/- Ly49 + Treg function whereas those that are associated with pathology promote naïve T cell and B cell accumulation. We hypothesize that CD8 +/- Ly49 + Tregs maintain self-tolerance after tissue damage and avert autoimmunity by eliminating naive T cells and preventing pathogenic B cell activation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":555877,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"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":1167609,"name":"Daphna Fertil","orcid":"0009-0000-0836-8406","position":1,"is_corresponding":false},{"id":823079,"name":"Devon R. Hartigan","orcid":null,"position":2,"is_corresponding":false},{"id":1344906,"name":"Paige Rudy","orcid":null,"position":3,"is_corresponding":false},{"id":322074,"name":"Sonakshi Sharma","orcid":null,"position":4,"is_corresponding":false},{"id":1178091,"name":"Toluwaleke D. Fashina","orcid":null,"position":5,"is_corresponding":false},{"id":1455236,"name":"Efua Maclean","orcid":null,"position":6,"is_corresponding":false},{"id":1455237,"name":"Alessandra B. Coogan","orcid":null,"position":7,"is_corresponding":false},{"id":629704,"name":"Tran B. Ngo","orcid":"0000-0002-4093-7004","position":8,"is_corresponding":false},{"id":1165705,"name":"Vanathi Sundaresan","orcid":null,"position":9,"is_corresponding":false},{"id":238245,"name":"Kaitlyn Sadtler","orcid":"0000-0003-2587-8330","position":10,"is_corresponding":false},{"id":337672,"name":"Aditya Josyula","orcid":"0000-0002-1184-0481","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T02:55:03.976486Z","pmid":"40568146","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":[]}