{"doi":"10.3389/fimmu.2022.912583","title":"Transcription Factor RUNX3 Mediates Plasticity of ThGM Cells Toward Th1 Phenotype","abstract":"GM-CSF-producing T helper (Th) cells play a crucial role in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). Recent studies have identified a distinct population of GM-CSF-producing Th cells, named ThGM cells, that also express cytokines TNF, IL-2, and IL-3, but lack expression of master transcription factors (TF) and signature cytokines of commonly recognized Th cell lineages. ThGM cells are highly encephalitogenic in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Similar to Th17 cells, in response to IL-12, ThGM cells upregulate expression of T-bet and IFN-γ and switch their phenotype to Th1. Here we show that in addition to T-bet, TF RUNX3 also contributes to the Th1 switch of ThGM cells. T-bet-deficient ThGM cells in the CNS of mice with EAE had low expression of RUNX3, and knockdown of RUNX3 expression in ThGM cells abrogated the Th1-inducing effect of IL-12. Comparison of ThGM and Th1 cell transcriptomes showed that ThGM cells expressed a set of TFs known to inhibit the development of other Th lineages. Lack of expression of lineage-specific cytokines and TFs by ThGM cells, together with expression of TFs that inhibit the development of other Th lineages, suggests that ThGM cells are a non-polarized subset of Th cells with lineage characteristics.","journal":"Frontiers in Immunology","year":2022,"id":272901,"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":11,"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":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":281011,"name":"Giacomo Casella","orcid":"0000-0002-1103-6303","position":1,"is_corresponding":false},{"id":281014,"name":"Weifeng Zhang","orcid":"0000-0002-6176-4907","position":2,"is_corresponding":false},{"id":281015,"name":"Dan Xiao","orcid":"0000-0003-3061-2289","position":3,"is_corresponding":false},{"id":281378,"name":"Gaurav Kumar","orcid":"0000-0001-5464-6518","position":4,"is_corresponding":false},{"id":328024,"name":"Paolo Fortina","orcid":"0000-0002-5898-2081","position":5,"is_corresponding":false},{"id":281022,"name":"Guang‐Xian Zhang","orcid":"0000-0003-0017-5997","position":6,"is_corresponding":false},{"id":281023,"name":"Bogoljub Ćirić","orcid":"0000-0001-5361-7635","position":7,"is_corresponding":false},{"id":281024,"name":"Abdolmohamad Rostami","orcid":"0000-0003-0716-2726","position":8,"is_corresponding":false},{"id":281012,"name":"Javad Rasouli","orcid":"0000-0002-0276-873X","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T00:27:52.048702Z","pmid":"35860266","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":[]}