{"doi":"10.1101/2020.06.01.128504","title":"ICOS signaling limits regulatory T cell accumulation and function in visceral adipose tissue","abstract":"Abstract A unique population of Foxp3 + regulatory T cells (T R ) resides in visceral adipose tissue (VAT) that regulates adipose inflammation and helps preserve insulin sensitivity. The costimulatory molecule ICOS is highly expressed on effector (e)T R that migrate to nonlymphoid tissues, and contributes to their maintenance and function in models of autoimmunity. In this study, we report an unexpected cell-intrinsic role for ICOS expression and downstream PI3K signaling in limiting the abundance, VAT-associated phenotype, and function of T R specifically in VAT. Icos −/− mice and mice expressing a knock-in form of ICOS that cannot activate PI3K had increased VAT-T R abundance and elevated expression of canonical VAT-T R markers. Loss of ICOS signaling facilitated enhanced accumulation of T R to VAT associated with elevated CCR3 expression, and resulted in reduced adipose inflammation and heightened insulin sensitivity in the context of high-fat diet. Thus, we have uncovered a new and surprising molecular pathway that regulates VAT-T R accumulation and function. Summary The authors demonstrate that loss of ICOS-dependent PI3-kinase signaling supports visceral adipose tissue (VAT) T R abundance and function, and this correlates with reduced adipose inflammation and improved insulin sensitivity after high-fat diet. This work highlights a new molecular pathway that regulates VAT-T R accumulation and activity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123762,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":567230,"name":"Erika Hayes","orcid":"0000-0002-2363-7253","position":1,"is_corresponding":false},{"id":108917,"name":"Daniel Campbell","orcid":"0000-0002-9652-7178","position":2,"is_corresponding":false},{"id":567229,"name":"Kristen Mittelsteadt","orcid":"0000-0002-4680-7585","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","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":[]}