{"doi":"10.4049/jimmunol.2300635","title":"Activin A Promotes Differentiation of a Pathogenic Multicytokine IL-9-secreting CD4+ T Cell Population","abstract":"The development of Th subsets results from cellular and cytokine cues that are present in the inflammatory environment. The developing T cell integrates multiple signals from the environment that sculpt the cytokine-producing capacity of the effector T cell. Importantly, T cells can discriminate similar cytokine signals to generate distinct outcomes, and that discrimination is critical in Th subset development. IL-9-secreting Th9 cells regulate multiple immune responses, including immunity to pathogens and tumors, allergic inflammation, and autoimmunity. In combination with IL-4, TGF-β or activin A promotes IL-9 production; yet, it is not clear if both TGF-β family members generate Th9 cells with identical phenotype and function. We observed that in contrast to TGF-β that efficiently represses Th2 cytokines in murine Th9 cultures, differentiation with activin A produced a multicytokine T cell phenotype with secretion of IL-4, IL-5, IL-13, and IL-10 in addition to IL-9. Moreover, multicytokine secreting cells are more effective at promoting allergic inflammation. These observations suggest that although TGF-β and IL-4 were identified as cytokines that stimulate optimal IL-9 production, they might not be the only cytokines that generate optimal function from IL-9-producing T cells in immunity and disease.","journal":"The Journal of Immunology","year":2024,"id":450447,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9447,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":944172,"name":"Wenwu Zhang","orcid":"0000-0002-4685-2458","position":1,"is_corresponding":false},{"id":1270553,"name":"Blake T. Kenworthy","orcid":"0000-0003-3338-3303","position":2,"is_corresponding":false},{"id":348767,"name":"Rakshin Kharwadkar","orcid":"0000-0002-6303-1651","position":3,"is_corresponding":false},{"id":1237003,"name":"Matthew R. Olson","orcid":"0000-0003-2351-6002","position":4,"is_corresponding":false},{"id":285837,"name":"Mark H. Kaplan","orcid":"0000-0002-2923-8245","position":5,"is_corresponding":false},{"id":348765,"name":"Benjamin J. Ulrich","orcid":"0000-0002-2729-1798","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:02:25.004119Z","pmid":"39058312","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":[]}