{"doi":"10.1101/2024.03.08.584164","title":"T cell cholesterol transport is a metabolic checkpoint that links intestinal immune responses to dietary lipid absorption","abstract":"The intrinsic pathways that control membrane organization in immune cells and the impact of such pathways on cellular function are not well defined. Here we report that the non-vesicular cholesterol transporter Aster-A links plasma membrane (PM) cholesterol availability in T cells to immune signaling and systemic metabolism. Aster-A is recruited to the PM during T-cell receptor (TCR) activation, where it facilitates the removal of newly generated \"accessible\" membrane cholesterol. Loss of Aster-A leads to excess PM cholesterol accumulation, resulting in enhanced TCR nano-clustering and signaling, and Th17 cytokine production. Finally, we show that the mucosal Th17 response is restrained by PM cholesterol remodeling. Ablation of Aster-A in T cells leads to enhanced IL-22 production, reduced intestinal fatty acid absorption, and resistance to diet-induced obesity. These findings delineate a multi-tiered regulatory scheme linking immune cell lipid flux to nutrient absorption and systemic physiology.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":488085,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9615,"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":343699,"name":"John P. Kennelly","orcid":"0000-0002-4399-3976","position":1,"is_corresponding":false},{"id":343700,"name":"Xiao Xu","orcid":"0000-0002-5033-7627","position":2,"is_corresponding":false},{"id":1026685,"name":"Emily Whang","orcid":"0000-0003-0704-6178","position":3,"is_corresponding":false},{"id":343697,"name":"Alessandra Ferrari","orcid":"0000-0001-7354-9895","position":4,"is_corresponding":false},{"id":292010,"name":"Alexander H. Bedard","orcid":"0000-0001-9208-398X","position":5,"is_corresponding":false},{"id":564715,"name":"Julia J. Mack","orcid":"0000-0002-9239-8436","position":6,"is_corresponding":false},{"id":897004,"name":"Alexander Nguyen","orcid":"0000-0001-6578-3454","position":7,"is_corresponding":false},{"id":328880,"name":"Thomas A. Weston","orcid":"0000-0003-3720-8633","position":8,"is_corresponding":false},{"id":1332599,"name":"Lauren F. Uchiyama","orcid":"0000-0002-6574-0064","position":9,"is_corresponding":false},{"id":1027435,"name":"Min Sub Lee","orcid":null,"position":10,"is_corresponding":false},{"id":268051,"name":"Stephen G. Young","orcid":"0000-0001-7270-3176","position":11,"is_corresponding":false},{"id":254569,"name":"Steven J. Bensinger","orcid":"0000-0002-9657-4206","position":12,"is_corresponding":false},{"id":246036,"name":"Peter Tontonoz","orcid":"0000-0003-1259-0477","position":13,"is_corresponding":false},{"id":367553,"name":"Yajing Gao","orcid":"0000-0002-8836-4452","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:15.008850Z","pmid":"38559079","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":[]}