{"doi":"10.1111/imm.13404","title":"IL‐33 activates mTORC1 and modulates glycolytic metabolism in CD8<sup>+</sup> T cells","abstract":"Abstract Interleukin (IL)‐33, a member in the IL‐1 family, plays a central role in innate and adaptive immunity; however, how IL‐33 mediates cytotoxic T‐cell regulation and the downstream signals remain elusive. In this study, we found increased mouse IL‐33 expression in CD8 + T cells following cell activation via anti‐CD3/CD28 stimulation in vitro or lymphocytic choriomeningitis virus (LCMV) infection in vivo . Our cell adoptive transfer experiment demonstrated that extracellular, but not nuclear, IL‐33 contributed to the activation and proliferation of CD8 + , but not CD4 + T effector cells in LCMV infection. Importantly, IL‐33 induced mTORC1 activation in CD8 + T cells as evidenced by increased phosphorylated S6 ribosomal protein (p‐S6) levels both in vitro and in vivo . Meanwhile, this IL‐33‐induced CD8 + T‐cell activation was suppressed by mTORC1 inhibitors. Furthermore, IL‐33 elevated glucose uptake and lactate production in CD8 + T cells in both dose‐ and time‐dependent manners. The results of glycolytic rate assay demonstrated the increased glycolytic capacity of IL‐33‐treated CD8 + T cells compared with that of control cells. Our mechanistic study further revealed the capacity of IL‐33 in promoting the expression of glucose transporter 1 (Glut1) and glycolytic enzymes via mTORC1, leading to accelerated aerobic glucose metabolism Warburg effect and increased effector T‐cell activation. Together, our data provide new insights into IL‐33‐mediated regulation of CD8 + T cells, which might be beneficial for therapeutic strategies of inflammatory and infectious diseases in the future.","journal":"Immunology","year":2021,"id":168769,"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":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9656,"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":698348,"name":"Xiaofang Wang","orcid":"0000-0003-2239-7080","position":1,"is_corresponding":false},{"id":698349,"name":"Hui Wang","orcid":"0000-0002-8706-2217","position":2,"is_corresponding":false},{"id":107264,"name":"Wenjing Yang","orcid":"0000-0003-1541-1892","position":3,"is_corresponding":false},{"id":427642,"name":"Panpan Yi","orcid":null,"position":4,"is_corresponding":false},{"id":426957,"name":"Lynn Soong","orcid":"0000-0003-3370-3434","position":5,"is_corresponding":false},{"id":107279,"name":"Yingzi Cong","orcid":"0000-0003-4167-7395","position":6,"is_corresponding":false},{"id":328833,"name":"Jiyang Cai","orcid":"0000-0003-4755-5452","position":7,"is_corresponding":false},{"id":693939,"name":"Xuegong Fan","orcid":"0000-0001-8081-348X","position":8,"is_corresponding":false},{"id":107270,"name":"Jiaren Sun","orcid":"0000-0001-5084-4437","position":9,"is_corresponding":false},{"id":426950,"name":"Yuejin Liang","orcid":"0000-0002-9557-1847","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:46:06.853307Z","pmid":"34411293","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":[]}