{"doi":"10.1038/s41586-024-08131-3","title":"Rhythmic IL-17 production by γδ T cells maintains adipose de novo lipogenesis","abstract":"The circadian rhythm of the immune system helps to protect against pathogens1–3; however, the role of circadian rhythms in immune homeostasis is less well understood. Innate T cells are tissue-resident lymphocytes with key roles in tissue homeostasis4–7. Here we use single-cell RNA sequencing, a molecular-clock reporter and genetic manipulations to show that innate IL-17-producing T cells—including γδ T cells, invariant natural killer T cells and mucosal-associated invariant T cells—are enriched for molecular-clock genes compared with their IFNγ-producing counterparts. We reveal that IL-17-producing γδ (γδ17) T cells, in particular, rely on the molecular clock to maintain adipose tissue homeostasis, and exhibit a robust circadian rhythm for RORγt and IL-17A across adipose depots, which peaks at night. In mice, loss of the molecular clock in the CD45 compartment (Bmal1∆Vav1) affects the production of IL-17 by adipose γδ17 T cells, but not cytokine production by αβ or IFNγ-producing γδ (γδIFNγ) T cells. Circadian IL-17 is essential for de novo lipogenesis in adipose tissue, and mice with an adipocyte-specific deficiency in IL-17 receptor C (IL-17RC) have defects in de novo lipogenesis. Whole-body metabolic analysis in vivo shows that Il17a−/−Il17f−/− mice (which lack expression of IL-17A and IL-17F) have defects in their circadian rhythm for de novo lipogenesis, which results in disruptions to their whole-body metabolic rhythm and core-body-temperature rhythm. This study identifies a crucial role for IL-17 in whole-body metabolic homeostasis and shows that de novo lipogenesis is a major target of IL-17. Innate IL-17-producing T cells—in particular, adipose γδ17 T cells—are enriched in molecular-clock genes, and the circadian expression of IL-17A and RORγt by these cells has a role in maintaining local homeostasis and regulating lipogenesis.","journal":"Nature","year":2024,"id":420325,"datarank":0.9143762551347348,"base_score":3.58351893845611,"endowment":3.58351893845611,"self_citation_contribution":0.5375278407684165,"citation_network_contribution":0.37684841436631816,"self_endowment_contribution":0.5375278407684165,"citer_contribution":0.37684841436631816,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":35,"citers_with_citation_signal":21,"citers_with_endowment":21,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9447,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE144255, GSE117468, GSE31652"]},"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":911991,"name":"Brenneth Stevens","orcid":null,"position":1,"is_corresponding":false},{"id":1211221,"name":"Miguel Rendas","orcid":"0000-0003-0755-9782","position":2,"is_corresponding":false},{"id":85074,"name":"Harry Kane","orcid":null,"position":3,"is_corresponding":false},{"id":1211222,"name":"Evan B. Lynch","orcid":"0009-0005-3577-4131","position":4,"is_corresponding":false},{"id":765410,"name":"Britta Kunkemoeller","orcid":"0000-0003-0709-1577","position":5,"is_corresponding":false},{"id":989334,"name":"Karl A. Wessendorf-Rodriguez","orcid":"0000-0002-4136-8771","position":6,"is_corresponding":false},{"id":642549,"name":"Emily A. Day","orcid":"0000-0003-3245-5715","position":7,"is_corresponding":false},{"id":354841,"name":"Caroline E. Sutton","orcid":null,"position":8,"is_corresponding":false},{"id":327443,"name":"Martin Brennan","orcid":null,"position":9,"is_corresponding":false},{"id":1202523,"name":"Katie O’Brien","orcid":"0000-0002-2414-635X","position":10,"is_corresponding":false},{"id":85071,"name":"Ayano C. Kohlgruber","orcid":"0000-0001-6758-3966","position":11,"is_corresponding":false},{"id":85077,"name":"Hannah Prendeville","orcid":"0000-0003-3731-4372","position":12,"is_corresponding":false},{"id":419655,"name":"Amanda Garza","orcid":"0000-0001-8557-8765","position":13,"is_corresponding":false},{"id":225198,"name":"Luke O'neill","orcid":"0000-0002-4333-2748","position":14,"is_corresponding":false},{"id":353711,"name":"Kingston H. G. Mills","orcid":"0000-0003-3646-8222","position":15,"is_corresponding":false},{"id":229039,"name":"Christian M. Metallo","orcid":"0000-0003-2404-3040","position":16,"is_corresponding":false},{"id":844245,"name":"Henrique Veiga‐Fernandes","orcid":"0000-0001-6216-1836","position":17,"is_corresponding":false},{"id":85084,"name":"Lydia Lynch","orcid":"0000-0002-4273-4681","position":18,"is_corresponding":false},{"id":85075,"name":"Aaron Douglas","orcid":"0000-0002-8812-9575","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T01:57:25.777459Z","pmid":"39478228","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":[]}