{"doi":"10.1126/sciadv.abm9120","title":"Differential metabolic requirement governed by transcription factor c-Maf dictates innate γδT17 effector functionality in mice and humans","abstract":"Cellular metabolism has been proposed to govern distinct γδ T cell effector functions, but the underlying molecular mechanisms remain unclear. We show that interleukin-17 (IL-17)-producing γδ T (γδT17) and interferon-γ (IFN-γ)-producing γδ T (γδT1) cells have differential metabolic requirements and that the rate-limiting enzyme isocitrate dehydrogenase 2 (IDH2) acts as a metabolic checkpoint for their effector functions. Intriguingly, the transcription factor c-Maf regulates γδT17 effector function through direct regulation of IDH2 promoter activity. Moreover, mTORC2 affects the expression of c-Maf and IDH2 and subsequent IL-17 production in γδ T cells. Deletion of c-Maf in γδ T cells reduces metastatic lung cancer development, suggesting c-Maf as a potential target for cancer immune therapy. We show that c-Maf also controls IL-17 production in human γδ T cells from peripheral blood and in oral cancers. These results demonstrate a critical role of the transcription factor c-Maf in regulating γδT17 effector function through IDH2-mediated metabolic reprogramming.","journal":"Science Advances","year":2022,"id":255378,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":903127,"name":"Yihua Cai","orcid":"0000-0002-7331-1200","position":1,"is_corresponding":false},{"id":903128,"name":"Xiaoling Hu","orcid":"0000-0001-9958-0727","position":2,"is_corresponding":false},{"id":250183,"name":"Chuanlin Ding","orcid":"0000-0001-9588-6403","position":3,"is_corresponding":false},{"id":250186,"name":"Liqing He","orcid":"0000-0002-0428-814X","position":4,"is_corresponding":false},{"id":250193,"name":"Xiang Zhang","orcid":"0000-0003-1102-6313","position":5,"is_corresponding":false},{"id":903129,"name":"Fuxiang Chen","orcid":"0000-0002-4093-2676","position":6,"is_corresponding":false},{"id":250194,"name":"Jun Yan","orcid":"0000-0003-2922-422X","position":7,"is_corresponding":false},{"id":903126,"name":"Xu Chen","orcid":"0000-0001-8840-0735","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T00:25:12.987829Z","pmid":"35613277","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":[]}