{"doi":"10.1016/j.isci.2020.101421","title":"The Cytokine Receptor IL-7Rα Impairs IL-2 Receptor Signaling and Constrains the In Vitro Differentiation of Foxp3+ Treg Cells","abstract":"Treg cells, however, express uniquely low amounts of the IL-7-proprietary IL-7Rα so that they are impaired in IL-7 signaling. Because Treg cells depend on IL-2, the loss of IL-7Rα has been considered irrelevant for Treg cells. In contrast, here, we report that IL-7Rα downregulation is necessary to maximize IL-2R signaling. Although IL-7Rα overexpression promoted IL-7 signaling, unexpectedly, IL-2 signaling was suppressed in the same cells. Mechanistically, we found that γc, which is a receptor subunit shared by IL-7R and IL-2R, directly binds and pre-associates with IL-7Rα, thus limiting its availability for IL-2R binding. Consequently, overexpression of signaling-deficient, tailless IL-7Rα proteins inhibited IL-2R signaling, demonstrating that IL-7Rα sequesters γc and suppresses IL-2R signaling by extracellular interactions. Collectively, these results reveal a previously unappreciated regulatory mechanism of IL-2 receptor signaling that is governed by IL-7Rα abundance.","journal":"iScience","year":2020,"id":97919,"datarank":0.5244761342199721,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.0,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"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":399862,"name":"Hilary R. Keller","orcid":"0000-0002-6510-5685","position":1,"is_corresponding":false},{"id":347694,"name":"Tae‐Hyoun Kim","orcid":"0000-0002-7949-6322","position":2,"is_corresponding":false},{"id":401028,"name":"Megan A. Luckey","orcid":null,"position":3,"is_corresponding":false},{"id":454552,"name":"Xuguang Tai","orcid":"0000-0001-5322-7127","position":4,"is_corresponding":false},{"id":483593,"name":"Changwan Hong","orcid":"0000-0003-2567-2973","position":5,"is_corresponding":false},{"id":374056,"name":"Carmen Molina-Parı́s","orcid":"0000-0001-9828-6737","position":6,"is_corresponding":false},{"id":399864,"name":"Scott T.R. Walsh","orcid":"0000-0002-9288-8443","position":7,"is_corresponding":false},{"id":399865,"name":"Jung‐Hyun Park","orcid":"0000-0002-9547-9055","position":8,"is_corresponding":false},{"id":471554,"name":"Adam T. Waickman","orcid":"0000-0002-4536-6714","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:36:02.818637Z","pmid":"32791329","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":[]}