{"doi":"10.1101/2022.09.02.506326","title":"WDFY4 deficiency in NOD mice abrogates autoimmune diabetes and insulitis","abstract":"Abstract The events that initiate autoimmune diabetes in NOD mice remain poorly understood. CD4 and CD8 T cells are both required but whether either cell initiates disease is unclear. To test whether CD4 T cell infiltration into islet required damage to β cells induced by autoreactive CD8 T cells, we selectively inactivated Wdfy4 in NOD mice (NOD. Wdfy4 -/- ) using CRISPR/Cas9 targeting. Similar to C57BL/6 Wdfy4 -/- mice NOD. Wdfy4 -/- mice develop type 1 conventional dendritic cells (cDC1) that are unable to cross-present cell-associated antigens required to activate CD8 T cells. By contrast, cDC1 from heterozygous Wdfy4 +/- mice can cross-present normally. Heterozygous NOD. Wdfy4 +/- mice develop diabetes similar to NOD mice, but NOD. Wdfy4 -/- mice neither develop diabetes nor prime autoreactive CD8 T cells in vivo . By contrast, NOD. Wdfy4 -/- mice can process and present MHC-II-restricted autoantigens and can activate β cell specific CD4 T cells in lymph nodes, and yet do not develop CD4 T cell infiltration in islets. These results indicate that the priming of autoreactive CD8 T cells in NOD mice requires cross-presentation by cDC1. Further, autoreactive CD8 T cells are 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":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":311145,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"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":634406,"name":"Jing Chen","orcid":"0000-0001-8008-8062","position":1,"is_corresponding":false},{"id":299072,"name":"Ray A. Ohara","orcid":"0000-0001-7897-3169","position":2,"is_corresponding":false},{"id":395806,"name":"Feiya Ou","orcid":"0000-0001-8289-4025","position":3,"is_corresponding":false},{"id":782545,"name":"Renee Wu","orcid":"0000-0002-9521-1657","position":4,"is_corresponding":false},{"id":299067,"name":"Sun Kyung Kim","orcid":"0000-0002-1375-6339","position":5,"is_corresponding":false},{"id":299070,"name":"Tiantian Liu","orcid":"0000-0001-9377-9938","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":24,"raw_metadata":null,"created_at":"2026-07-19T00:33:28.480200Z","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":[]}