{"doi":"10.1172/jci95837","title":"γδTCR recruits the Syk/PI3K axis to drive proinflammatory differentiation program","abstract":null,"journal":"Journal of Clinical Investigation","year":2017,"id":660863,"datarank":0.6064576901751826,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":0.0,"self_endowment_contribution":0.6064576901751826,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":754492,"name":"Takeshi Nitta","orcid":"0000-0003-2384-3062","position":1,"is_corresponding":false},{"id":1033072,"name":"Kenta Nakano","orcid":"0000-0003-2617-1468","position":2,"is_corresponding":false},{"id":299091,"name":"Tadashi Okamura","orcid":"0000-0001-8457-1561","position":3,"is_corresponding":false},{"id":754493,"name":"Hiroshi Takayanagi","orcid":"0000-0002-1462-4127","position":4,"is_corresponding":false},{"id":1276788,"name":"Harumi Suzuki","orcid":"0000-0003-3616-9361","position":5,"is_corresponding":false},{"id":755264,"name":"Ryunosuke Muro","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"γδTCR recruits the Syk/PI3K axis to drive proinflammatory differentiation program","abstract":"γδT cells produce inflammatory cytokines and have been implicated in the pathogenesis of cancer, infectious diseases, and autoimmunity. The T cell receptor (TCR) signal transduction that specifically regulates the development of IL-17-producing γδT (γδT17) cells largely remains unclear. Here, we showed that the receptor proximal tyrosine kinase Syk is essential for γδTCR signal transduction and development of γδT17 in the mouse thymus. Zap70, another tyrosine kinase essential for the development of αβT cells, failed to functionally substitute for Syk in the development of γδT17. Syk induced the activation of the PI3K/Akt pathway upon γδTCR stimulation. Mice deficient in PI3K signaling exhibited a complete loss of γδT17, without impaired development of IFN-γ-producing γδT cells. Moreover, γδT17-dependent skin inflammation was ameliorated in mice deficient in RhoH, an adaptor known to recruit Syk. Thus, we deciphered lineage-specific TCR signaling and identified the Syk/PI3K pathway as a critical determinant of proinflammatory γδT cell differentiation.","is_dataset_classified":null,"base_score":4.04305126783455,"endowment":4.04305126783455,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29202478","pmcid":"PMC5749532","openalex_id":"https://openalex.org/W2772946027","authors":[],"funders":[{"funder_name":"The National Center for Global Health and Medicine","grant_id":"26A-105","title":null},{"funder_name":"The Kanehara-Ichiro Foundation","grant_id":"29-23","title":null},{"funder_name":"The Japan Society for Promotion of Science (JSPS)","grant_id":"KAKENHI 15H05703","title":null},{"funder_name":"The Japan Society for Promotion of Science (JSPS)","grant_id":"16H05202","title":null},{"funder_name":"The Japan Society for Promotion of Science (JSPS)","grant_id":"16K19102","title":null}],"total_grants":5,"fwci":1.2972,"citation_percentile":0.79126991,"influential_citations":0,"citation_trend":[{"year":2018,"count":3},{"year":2019,"count":5},{"year":2020,"count":5},{"year":2021,"count":7},{"year":2022,"count":10},{"year":2023,"count":3},{"year":2024,"count":7},{"year":2025,"count":9},{"year":2026,"count":7}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"http://www.jci.org/articles/view/95837/files/pdf","host_type":"journal"},{"url":"http://www.jci.org/articles/view/95837/files/pdf","host_type":"publisher"},{"url":"https://www.jci.org/articles/view/95837/files/pdf","host_type":"publisher"},{"url":"https://doi.org/10.1172/jci95837","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29202478","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5749532","host_type":"repository"}],"fields_of_study":["T-cell and B-cell Immunology","Immune Response and Inflammation","Immune Cell Function and Interaction"],"mesh_terms":["Syk Kinase","Animals","Cell Differentiation","Inflammation","Interferon-gamma","Signal Transduction","Receptors, Antigen, T-Cell, gamma-delta","Mice, Knockout","Phosphatidylinositol 3-Kinases","Proto-Oncogene Proteins c-akt","Mice","Th17 Cells"],"keywords":["Syk","Proinflammatory cytokine","ZAP70","PI3K/AKT/mTOR pathway","T-cell receptor","Signal transduction","Cell biology","Biology","Tyrosine kinase","Cancer research","T cell","Protein kinase B","Signal transducing adaptor protein","Immunology","Inflammation","Immune system","Cytokines","T Cell Development"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T10:01:40.508891Z","pmid":null,"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":[]}