{"doi":"10.3389/fimmu.2021.642856","title":"The Timing and Abundance of IL-2Rβ (CD122) Expression Control Thymic iNKT Cell Generation and NKT1 Subset Differentiation","abstract":"Invariant NKT ( i NKT) cells are thymus-generated innate-like T cells, comprised of three distinct subsets with divergent effector functions. The molecular mechanism that drives the lineage trifurcation of immature i NKT cells into the NKT1, NKT2, and NKT17 subsets remains a controversial issue that remains to be resolved. Because cytokine receptor signaling is necessary for i NKT cell generation, cytokines are proposed to contribute to i NKT subset differentiation also. However, the precise roles and requirements of cytokines in these processes are not fully understood. Here, we show that IL-2Rβ, a nonredundant component of the IL-15 receptor complex, plays a critical role in both the development and differentiation of thymic i NKT cells. While the induction of IL-2Rβ expression on postselection thymocytes is necessary to drive the generation of i NKT cells, surprisingly, premature IL-2Rβ expression on immature i NKT cells was detrimental to their development. Moreover, while IL-2Rβ is necessary for NKT1 generation, paradoxically, we found that the increased abundance of IL-2Rβ suppressed NKT1 generation without affecting NKT2 and NKT17 cell differentiation. Thus, the timing and abundance of IL-2Rβ expression control i NKT lineage fate and development, thereby establishing cytokine receptor expression as a critical regulator of thymic i NKT cell differentiation.","journal":"Frontiers in Immunology","year":2021,"id":179424,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"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":510159,"name":"Hye Kyung Kim","orcid":"0009-0005-4043-4406","position":1,"is_corresponding":false},{"id":399863,"name":"Assiatu Crossman","orcid":"0000-0001-5746-0073","position":2,"is_corresponding":false},{"id":262758,"name":"Parirokh Awasthi","orcid":"0000-0002-5831-9781","position":3,"is_corresponding":false},{"id":233605,"name":"Ronald E. Gress","orcid":"0000-0001-8259-5332","position":4,"is_corresponding":false},{"id":399865,"name":"Jung‐Hyun Park","orcid":"0000-0002-9547-9055","position":5,"is_corresponding":false},{"id":726896,"name":"Hee Yeun Won","orcid":"0000-0001-5830-0354","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:47:48.974996Z","pmid":"34054809","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":[]}