{"doi":"10.1101/2024.03.12.584692","title":"The β2-adrenergic receptor (ADRB2) entrains circadian gene oscillation and diurnal responses to virus infection in CD8 <sup>+</sup> T cells","abstract":"Abstract Adaptive immune cells are regulated by circadian rhythms (CR) under both steady state conditions and during responses to infection. Cytolytic CD8 + T cells display variable responses to infection depending upon the time of day of exposure. However, the neuronal signals that entrain these cyclic behaviors remain unknown. Immune cells express a variety of neurotransmitter receptors including nicotinic, glucocorticoid, and adrenergic receptors. Here, we demonstrate that the β2-adrenergic receptor (ADRB2) regulates the periodic oscillation of select core clock genes, such as Per2 and Bmal1 , and selective loss of the Adrb2 gene dramatically perturbs the normal diurnal oscillation of clock gene expression in CD8 + T cells. Consequently, their circadian-regulated anti-viral response is dysregulated, and the diurnal development of CD8 + T cells into variegated populations of cytolytic T cell (CTL) effectors is dramatically altered in the absence of ADRB2 signaling. Thus, the Adrb2 directly entrains core clock gene oscillation and regulates CR-dependent T cell responses to virus infection as a function of time-of-day of pathogen exposure. One Sentence Summary The β2-adrenergic receptor regulates circadian gene oscillation and downstream daily timing of cytolytic T cell responses to virus infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":495275,"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":0.9605,"is_data_producer":false,"deposit_databanks":null,"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":1341971,"name":"Kira A. Kohlbach","orcid":null,"position":1,"is_corresponding":false},{"id":724490,"name":"Robert W. Maples","orcid":"0000-0002-5815-1210","position":2,"is_corresponding":false},{"id":249100,"name":"David J. Farrar","orcid":"0000-0001-8584-7080","position":3,"is_corresponding":false},{"id":249099,"name":"Drashya Sharma","orcid":"0000-0003-0309-7779","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:09:15.528853Z","pmid":"38559276","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":[]}