{"doi":"10.3389/fimmu.2021.810080","title":"Phenotypic and Functional Plasticity of CXCR6+ Peripheral Blood NK Cells","abstract":"Human NK cells are comprised of phenotypic subsets, whose potentially unique functions remain largely unexplored. C-X-C-motif-chemokine-receptor-6 (CXCR6) + NK cells have been identified as phenotypically immature tissue-resident NK cells in mice and humans. A small fraction of peripheral blood (PB)-NK cells also expresses CXCR6. However, prior reports about their phenotypic and functional plasticity are conflicting. In this study, we isolated, expanded, and phenotypically and functionally evaluated CXCR6 + and CXCR6 – PB-NK cells, and contrasted results to bulk liver and spleen NK cells. We found that CXCR6 + and CXCR6 – PB-NK cells preserved their distinct phenotypic profiles throughout 14 days of in vitro expansion (“day 14”), after which phenotypically immature CXCR6 + PB-NK cells became functionally equivalent to CXCR6 – PB-NK cells. Despite a consistent reduction in CD16 expression and enhanced expression of the transcription factor Eomesodermin (Eomes), day 14 CXCR6 + PB-NK cells had superior antibody-dependent cellular cytotoxicity (ADCC) compared to CXCR6 – PB-NK cells. Further, bulk liver NK cells responded to IL-15, but not IL-2 stimulation, with STAT-5 phosphorylation. In contrast, bulk splenic and PB-NK cells robustly responded to both cytokines. Our findings may allow for the selection of superior NK cell subsets for infusion products increasingly used to treat human diseases.","journal":"Frontiers in Immunology","year":2022,"id":272396,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"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":227894,"name":"Graham D. Hogg","orcid":"0000-0002-7143-0695","position":1,"is_corresponding":false},{"id":703742,"name":"Shawn Abeynaike","orcid":"0000-0002-0346-624X","position":2,"is_corresponding":false},{"id":639064,"name":"Lynn Bimler","orcid":"0000-0002-7473-9698","position":3,"is_corresponding":false},{"id":281959,"name":"Alexander Vargas‐Hernández","orcid":"0000-0002-8409-4862","position":4,"is_corresponding":false},{"id":267158,"name":"Silke Paust","orcid":"0000-0002-0526-3999","position":5,"is_corresponding":false},{"id":757690,"name":"Laura S. Angelo","orcid":null,"position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-19T00:27:47.926496Z","pmid":"35173710","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":[]}