{"doi":"10.1101/2021.01.19.427356","title":"NF-kB c-Rel is dispensable for the development but is required for the cytotoxic function of NK cells","abstract":"Abstract Natural Killer (NK) cells are cytotoxic lymphocytes critical to the innate immune system. We found that germline deficiency of NF-kB c-Rel results in a marked decrease in cytotoxic function of NK cells, both in vitro and in vivo, with no significant differences in the stages of NK cell development. We found that c-Rel binds to the promoters of perforin and granzyme B, two key proteins required for NK cytotoxicity, and controls their transactivation. We generated a NK cell specific c-Rel conditional knockout to study NK cell intrinsic role of c-Rel and found that both global and conditional c-Rel deficiency leads to decreased perforin and granzyme B expression and thereby cytotoxic function. We also confirmed the role of c-Rel in perforin and granzyme B expression in human NK cells. c-Rel reconstitution rescued perforin and granzyme B expressions in c-Rel deficient NK cells and restored their cytotoxic function. Our results show a previously unknown role of c-Rel in transcriptional regulation of perforin and granzyme B expressions and control of NK cell cytotoxic function.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220090,"datarank":0.13518007004053928,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.031207992956547477,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.031207992956547477,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":146780,"name":"K ZHANG","orcid":null,"position":1,"is_corresponding":false},{"id":326799,"name":"Parameswaran Ramakrishnan","orcid":"0000-0002-1314-827X","position":2,"is_corresponding":false},{"id":749328,"name":"Reshmi Parameswaran","orcid":"0000-0002-8043-7450","position":3,"is_corresponding":false},{"id":750254,"name":"Yorleny Vicioso","orcid":null,"position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:42.928212Z","pmid":null,"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":[]}