{"doi":"10.1089/ars.2022.0058","title":"T Cell <i>Nrf2/Keap1</i> Gene Editing Using CRISPR/Cas9 and Experimental Kidney Ischemia-Reperfusion Injury","abstract":"Aims: T cells play pathophysiologic roles in kidney ischemia-reperfusion injury (IRI), and the nuclear factor erythroid 2-related factor 2/kelch-like ECH-associated protein 1 (Nrf2/Keap1) pathway regulates T cell responses. We hypothesized that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated Keap1 -knockout (KO) augments Nrf2 antioxidant potential of CD4+ T cells, and that Keap1 -KO CD4+ T cell immunotherapy protects from kidney IRI. Results: CD4+ T cell Keap1 -KO resulted in significant increase of Nrf2 target genes NAD(P)H quinone dehydrogenase 1, heme oxygenase 1, glutamate-cysteine ligase catalytic subunit, and glutamate-cysteine ligase modifier subunit. Keap1 -KO cells displayed no signs of exhaustion, and had significantly lower levels of interleukin 2 (IL2) and IL6 in normoxic conditions, but increased interferon gamma in hypoxic conditions in vitro . In vivo , adoptive transfer of Keap1 -KO CD4+ T cells before IRI improved kidney function in T cell-deficient nu/nu mice compared with mice receiving unedited control CD4+ T cells. Keap1 -KO CD4+ T cells isolated from recipient kidneys 24 h post IR were less activated compared with unedited CD4+ T cells, isolated from control kidneys. Innovation: Editing Nrf2/Keap1 pathway in murine T cells using CRISPR/Cas9 is an innovative and promising immunotherapy approach for kidney IRI and possibly other solid organ IRI. Conclusion: CRISPR/Cas9-mediated Keap1 -KO increased Nrf2-regulated antioxidant gene expression in murine CD4+ T cells, modified responses to in vitro hypoxia and in vivo kidney IRI. Gene editing targeting the Nrf2/Keap1 pathway in T cells is a promising approach for immune-mediated kidney diseases.","journal":"Antioxidants and Redox Signaling","year":2023,"id":336873,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":350849,"name":"Sanjeev Noel","orcid":"0000-0001-9818-1177","position":1,"is_corresponding":false},{"id":799019,"name":"Kyungho Lee","orcid":"0000-0003-2627-0220","position":2,"is_corresponding":false},{"id":350848,"name":"Mohanraj Sadasivam","orcid":"0000-0002-3132-2948","position":3,"is_corresponding":false},{"id":1056600,"name":"Sepideh Gharaie","orcid":null,"position":4,"is_corresponding":false},{"id":408231,"name":"Aparna Ankireddy","orcid":null,"position":5,"is_corresponding":false},{"id":1067822,"name":"Sul A Lee","orcid":"0000-0003-2121-721X","position":6,"is_corresponding":false},{"id":1067823,"name":"Andrea M. Newman-Rivera","orcid":"0000-0002-2032-4438","position":7,"is_corresponding":false},{"id":680261,"name":"Jing Gong","orcid":"0000-0002-5061-4401","position":8,"is_corresponding":false},{"id":680518,"name":"Lois J. Arend","orcid":"0000-0001-5434-7630","position":9,"is_corresponding":false},{"id":352220,"name":"Abdel R.A. Hamad","orcid":null,"position":10,"is_corresponding":false},{"id":407355,"name":"Sekhar P. Reddy","orcid":"0000-0001-5027-9175","position":11,"is_corresponding":false},{"id":350850,"name":"Hamid Rabb","orcid":"0000-0002-4761-1103","position":12,"is_corresponding":false},{"id":350847,"name":"Johanna T. Kurzhagen","orcid":"0000-0001-6904-0746","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T01:10:21.947540Z","pmid":"36734409","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":[]}