{"doi":"10.1126/sciadv.abk3327","title":"Extracellular matrix proteins regulate NK cell function in peripheral tissues","abstract":"Natural killer (NK) cells reject major histocompatibility complex class I (MHC-I)-deficient bone marrow through direct cytotoxicity but not solid organ transplants devoid of MHC-I. Here, we demonstrate an immediate switch in NK cell function upon exit from the circulation, characterized by a shift from direct cytotoxicity to chemokine/cytokine production. In the skin transplant paradigm, combining an NK cell-specific activating ligand, m157, with missing self MHC-I resulted in complete graft rejection, which was dependent on NK cells as potential helpers and T cells as effectors. Extracellular matrix proteins, collagen I, collagen III, and elastin, blocked NK cell cytotoxicity and promoted their chemokine/cytokine production. NK cell cytotoxicity against MHC-I-deficient melanoma in the skin was markedly increased by blocking tumor collagen deposition. MHC-I down-regulation occurred in solid human cancers but not leukemias, which could be directly targeted by circulating cytotoxic NK cells. Our findings uncover a fundamental mechanism that restricts direct NK cell cytotoxicity in peripheral tissues.","journal":"Science Advances","year":2022,"id":237192,"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":62,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":859026,"name":"Maulik Vyas","orcid":"0000-0003-2996-4682","position":1,"is_corresponding":false},{"id":859027,"name":"Marta Requesens","orcid":"0000-0001-5559-8845","position":2,"is_corresponding":false},{"id":270393,"name":"Adam Langenbucher","orcid":"0000-0002-6291-580X","position":3,"is_corresponding":false},{"id":753616,"name":"Erik B. Schiferle","orcid":"0000-0002-3998-7530","position":4,"is_corresponding":false},{"id":16001,"name":"Robert T. Manguso","orcid":"0000-0003-1336-413X","position":5,"is_corresponding":false},{"id":1755,"name":"Michael S. Lawrence","orcid":"0000-0002-1307-459X","position":6,"is_corresponding":false},{"id":441396,"name":"Shadmehr Demehri","orcid":"0000-0002-7913-2641","position":7,"is_corresponding":false},{"id":859025,"name":"Mark D. Bunting","orcid":"0000-0002-7575-4910","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T00:22:08.925400Z","pmid":"35294229","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":[]}