{"doi":"10.4049/jimmunol.1901082","title":"Critical Role for SLAM/SAP Signaling in the Thymic Developmental Programming of IL-17– and IFN-γ–Producing γδ T Cells","abstract":"Abstract During thymic development, mouse γδ T cells commit to either an IFN-γ– or an IL-17–producing phenotype through mechanisms that remain unclear. In this study, we investigated the extent to which the SLAM/SAP signaling pathway regulates the functional programming of γδ T cells. Characterization of SLAM family receptor expression revealed that thymic γδ T cell subsets were each marked by distinct coexpression profiles of SLAMF1, SLAMF4, and SLAMF6. In the thymus, Vγ1 and Vγ4 T cells that exhibited an SLAMF1+SLAMF6+ double positive phenotype were largely contained within immature CD24+CD73− and CD24+CD73+ subsets, whereas SLAMF1 single positive, SLAMF6 single positive, or SLAMF1SLAMF6 double negative cells were found within mature CD24−CD73+ and CD24−CD73− subsets. In the periphery, SLAMF1 and SLAMF6 expression distinguished IL-17– and IFN-γ–producing γδ T cells, respectively. Disruption of SLAM family receptor signaling through deletion of SAP resulted in impaired thymic Vγ1 and Vγ4 T cell maturation at the CD24+CD73−SLAMF1+SLAMF6+ double positive stage that was associated with a decreased frequency of CD44+RORγt+ γδ T cells. Impaired development was in turn associated with decreased γδ T cell IL-17 and IFN-γ production in the thymus as well as in peripheral tissues. The role for SAP was subset-specific, as Vγ1Vδ6.3, Vγ4, Vγ5, but not Vγ6 subsets were SAP-dependent. Together, these data suggest that the SLAM/SAP signaling pathway plays a larger role in γδ T cell development than previously appreciated and represents a critical checkpoint in the functional programming of both IL-17– and IFN-γ–producing γδ T cell subsets.","journal":"The Journal of Immunology","year":2020,"id":105261,"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":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9463,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":510836,"name":"Victoria L. DeVault","orcid":null,"position":1,"is_corresponding":false},{"id":509764,"name":"Shawn C. Musial","orcid":"0000-0002-4146-1503","position":2,"is_corresponding":false},{"id":509765,"name":"Somen K Mistri","orcid":"0000-0002-2139-6927","position":3,"is_corresponding":false},{"id":510837,"name":"Linda Mei","orcid":null,"position":4,"is_corresponding":false},{"id":510838,"name":"Aleksandr Baraev","orcid":null,"position":5,"is_corresponding":false},{"id":246861,"name":"Julie A. Dragon","orcid":"0000-0002-8031-5381","position":6,"is_corresponding":false},{"id":270822,"name":"Dimitry N. Krementsov","orcid":"0000-0003-2709-7466","position":7,"is_corresponding":false},{"id":274437,"name":"André Veillette","orcid":"0000-0003-1159-4345","position":8,"is_corresponding":false},{"id":356384,"name":"Jonathan E. Boyson","orcid":"0000-0003-2673-9148","position":9,"is_corresponding":false},{"id":509763,"name":"Oliver Dienz","orcid":"0000-0001-9380-4873","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T23:12:17.683386Z","pmid":"32024701","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":[]}