{"doi":"10.1172/jci.insight.149656","title":"The small intestine epithelium exempts Foxp3+ Tregs from their IL-2 requirement for homeostasis and effector function","abstract":"Foxp3+ Tregs are potent immunosuppressive CD4+ T cells that are critical to maintain immune quiescence and prevent autoimmunity. Both the generation and maintenance of Foxp3+ Tregs depend on the cytokine IL-2. Hence, the expression of the IL-2 receptor α-chain (CD25) is not only considered a specific marker, but also a nonredundant requirement for Tregs. Here, we report that Foxp3+ Tregs in the small intestine (SI) epithelium, a critical barrier tissue, are exempt from such an IL-2 requirement, since they had dramatically downregulated CD25 expression, showed minimal STAT5 phosphorylation ex vivo, and were unable to respond to IL-2 in vitro. Nonetheless, SI epithelial Tregs survived and were present at the same frequency as in other lymphoid organs, and they retained potent suppressor function that was associated with high levels of CTLA-4 expression and the production of copious amounts of IL-10. Moreover, adoptive transfer experiments of Foxp3+ Tregs revealed that such IL-2-independent survival and effector functions were imposed by the SI epithelial tissue, suggesting that tissue adaptation is a mechanism that tailors the effector function and survival requirements of Foxp3+ Tregs specific to the tissue environment.","journal":"JCI Insight","year":2021,"id":188731,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9401,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":750598,"name":"Jaylene Alvarez-DelValle","orcid":null,"position":1,"is_corresponding":false},{"id":399862,"name":"Hilary R. Keller","orcid":"0000-0002-6510-5685","position":2,"is_corresponding":false},{"id":399863,"name":"Assiatu Crossman","orcid":"0000-0001-5746-0073","position":3,"is_corresponding":false},{"id":454552,"name":"Xuguang Tai","orcid":"0000-0001-5322-7127","position":4,"is_corresponding":false},{"id":750005,"name":"Yoo Kyoung Park","orcid":"0000-0002-8536-0835","position":5,"is_corresponding":false},{"id":399865,"name":"Jung‐Hyun Park","orcid":"0000-0002-9547-9055","position":6,"is_corresponding":false},{"id":399861,"name":"Praveen Prakhar","orcid":"0000-0001-8726-7397","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:49:10.350554Z","pmid":"34747370","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":[]}