{"doi":"10.1172/jci.insight.171830","title":"IFN-λ uniquely promotes CD8 T cell immunity against SARS-CoV-2 relative to type I IFN","abstract":"Optimization of protective immune responses against SARS-CoV-2 remains an urgent worldwide priority. In this regard, type III IFN (IFN-λ) restricts SARS-CoV-2 infection in vitro, and treatment with IFN-λ limits infection, inflammation, and pathogenesis in murine models. Furthermore, IFN-λ has been developed for clinical use to limit COVID-19 severity. However, whether endogenous IFN-λ signaling has an effect on SARS-CoV-2 antiviral immunity and long-term immune protection in vivo is unknown. In this study, we identified a requirement for IFN-λ signaling in promoting viral clearance and protective immune programming in SARS-CoV-2 infection of mice. Expression of both IFN and IFN-stimulated gene (ISG) in the lungs were minimally affected by the absence of IFN-λ signaling and correlated with transient increases in viral titers. We found that IFN-λ supported the generation of protective CD8 T cell responses against SARS-CoV-2 by facilitating accumulation of CD103+ DC in lung draining lymph nodes (dLN). IFN-λ signaling specifically in DCs promoted the upregulation of costimulatory molecules and the proliferation of CD8 T cells. Intriguingly, antigen-specific CD8 T cell immunity to SARS-CoV-2 was independent of type I IFN signaling, revealing a nonredundant function of IFN-λ. Overall, these studies demonstrate a critical role for IFN-λ in protective innate and adaptive immunity upon infection with SARS-CoV-2 and suggest that IFN-λ serves as an immune adjuvant to support CD8 T cell immunity.","journal":"JCI Insight","year":2024,"id":436965,"datarank":0.3889519153769944,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.016215917908794276,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.016215917908794276,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":8,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9447,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE253635"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":813243,"name":"Parker Denz","orcid":"0000-0001-9420-1337","position":1,"is_corresponding":false},{"id":241036,"name":"Adam D. Kenney","orcid":"0000-0002-9110-1178","position":2,"is_corresponding":false},{"id":807367,"name":"Najmus Mahfooz","orcid":null,"position":3,"is_corresponding":false},{"id":822589,"name":"Samuel Speaks","orcid":"0009-0003-7610-1502","position":4,"is_corresponding":false},{"id":1245785,"name":"Qiaoke Gong","orcid":null,"position":5,"is_corresponding":false},{"id":241041,"name":"Richard Robinson","orcid":"0000-0002-4699-515X","position":6,"is_corresponding":false},{"id":486467,"name":"Matthew E. Long","orcid":"0000-0003-4485-019X","position":7,"is_corresponding":false},{"id":335063,"name":"Adriana Forero","orcid":"0000-0002-2698-658X","position":8,"is_corresponding":false},{"id":241044,"name":"Jacob S. Yount","orcid":"0000-0002-6128-4575","position":9,"is_corresponding":false},{"id":108904,"name":"Emily A. Hemann","orcid":"0000-0002-6398-3492","position":10,"is_corresponding":false},{"id":1163579,"name":"Abigail Solstad","orcid":"0000-0002-9175-4275","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T02:00:16.989773Z","pmid":"38973611","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":[]}