{"doi":"10.1172/jci.insight.191359","title":"Single-cell transcriptional analysis reveals allergen-specific signatures in human γδ T cells","abstract":"The role of gamma-delta T (γδ T) cells in immune responses to common allergens is poorly understood. Here, we utilized single-cell (sc) transcriptomic analysis of allergen-reactive γδ T cells in humans to characterize the transcriptional landscapes and TCR repertoires in response to cockroach (CR) and mouse (MO) allergens. Using a potentially novel activation-induced marker (AIM) assay that allows detection of γδ T cells combined with scRNA sequencing and TCR repertoire analysis, we identified both shared and allergen-specific γδ T cell activation patterns and gene expression profiles. While CR extract activated both Vδ1 and Vδ2 subsets, MO extract primarily stimulated Vδ2 cells. Our analysis revealed allergen-specific clusters with distinct functional signatures, including enhanced inflammatory responses and cytotoxic effector functions in MO-specific γδ T cells and natural killer cell-mediated immunity and IFN-γ signaling in CR-specific populations. Comparison of allergic and nonallergic individuals highlighted differences in gene expression and TCR repertoires, including a higher IFNG expression in the CR-allergic compared with nonallergic cohorts, suggesting that phenotypic and functional differences are associated with γδ T allergen responses. This study provides insights into the cellular and molecular heterogeneity and functionality of allergen-reactive γδ T cells, offering a foundation for understanding their role in allergic diseases and potential therapeutic interventions.","journal":"JCI Insight","year":2025,"id":525549,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":429018,"name":"Sloan A. Lewis","orcid":"0000-0001-9025-7122","position":1,"is_corresponding":false},{"id":106293,"name":"Esther Dawen Yu","orcid":"0000-0002-3970-3753","position":2,"is_corresponding":false},{"id":1049113,"name":"Adam Abawi","orcid":null,"position":3,"is_corresponding":false},{"id":615292,"name":"Eric Wang","orcid":"0000-0002-2378-9505","position":4,"is_corresponding":false},{"id":1065423,"name":"Synaida Maiche","orcid":null,"position":5,"is_corresponding":false},{"id":852053,"name":"Monalisa Mondal","orcid":null,"position":6,"is_corresponding":false},{"id":110385,"name":"Pandurangan Vijayanand","orcid":"0000-0001-7067-9723","position":7,"is_corresponding":false},{"id":110383,"name":"Grégory Seumois","orcid":"0000-0002-8164-6852","position":8,"is_corresponding":false},{"id":34766,"name":"Bjoern Peters","orcid":"0000-0002-8457-6693","position":9,"is_corresponding":false},{"id":55670,"name":"Alessandro Sette","orcid":"0000-0001-7013-2250","position":10,"is_corresponding":false},{"id":106294,"name":"Ricardo da Silva Antunes","orcid":"0000-0001-9785-5272","position":11,"is_corresponding":false},{"id":811337,"name":"Kendall Kearns","orcid":"0000-0002-4633-4554","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:50:21.274116Z","pmid":"40244697","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":[]}