{"doi":"10.1073/pnas.2219956120","title":"WDFY4 deficiency in NOD mice ameliorates autoimmune diabetes and insulitis","abstract":"The events that initiate autoimmune diabetes in nonobese diabetic (NOD) mice remain poorly understood. CD4 + and CD8 + T cells are both required to develop disease, but their relative roles in initiating disease are unclear. To test whether CD4 + T cell infiltration into islets requires damage to β cells induced by autoreactive CD8 + T cells, we inactivated Wdfy4 in nonobese diabetic (NOD) mice (NOD. Wdfy4 −/−- ) using CRISPR/Cas9 targeting to eliminate cross-presentation by type 1 conventional dendritic cells (cDC1s). Similar to C57BL/6 Wdfy4 −/− mice, cDC1 in NOD. Wdfy4 −/− mice are unable to cross-present cell-associated antigens to prime CD8 + T cells, while cDC1 from heterozygous NOD. Wdfy4 +/− mice cross-present normally. Further, NOD. Wdfy4 −/− mice fail to develop diabetes while heterozygous NOD. Wdfy4 +/− mice develop diabetes similarly to wild-type NOD mice. NOD. Wdfy4 −/− mice remain capable of processing and presenting major histocompatibility complex class II (MHC-II)-restricted autoantigens and can activate β cell-specific CD4 + T cells in lymph nodes. However, disease in these mice does not progress beyond peri-islet inflammation. These results indicate that the priming of autoreactive CD8 + T cells in NOD mice requires cross-presentation by cDC1. Further, autoreactive CD8 + T cells appear to be required not only to develop diabetes, but to recruit autoreactive CD4 + T cells into islets of NOD mice, perhaps in response to progressive β cell damage.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":330198,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"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":299070,"name":"Tiantian Liu","orcid":"0000-0001-9377-9938","position":1,"is_corresponding":false},{"id":634406,"name":"Jing Chen","orcid":"0000-0001-8008-8062","position":2,"is_corresponding":false},{"id":299072,"name":"Ray A. Ohara","orcid":"0000-0001-7897-3169","position":3,"is_corresponding":false},{"id":395806,"name":"Feiya Ou","orcid":"0000-0001-8289-4025","position":4,"is_corresponding":false},{"id":782545,"name":"Renee Wu","orcid":"0000-0002-9521-1657","position":5,"is_corresponding":false},{"id":299067,"name":"Sun Kyung Kim","orcid":"0000-0002-1375-6339","position":6,"is_corresponding":false},{"id":299074,"name":"Theresa L. Murphy","orcid":"0000-0001-6539-8142","position":7,"is_corresponding":false},{"id":227901,"name":"Kenneth M. Murphy","orcid":"0000-0002-3505-9630","position":8,"is_corresponding":false},{"id":699735,"name":"Stephen T. Ferris","orcid":"0000-0003-3340-2607","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T01:09:10.120703Z","pmid":"36940342","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":[]}