{"doi":"10.1016/j.ebiom.2025.105578","title":"Decreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome","abstract":"Background The 17q12 deletion syndrome (17q12DS) is a heterozygous deletion of a 1.4 megabase‒spanning DNA sequence on chromosome 17. The clinical characteristics of 17q12DS include neurodevelopmental disorders, kidney and urinary tract abnormalities. In our cohort of 37 subjects with 17q12DS, we observed increased atopic disorders and recurrent sinopulmonary infections, raising the possibility of immune dysregulation in 17q12DS, a feature that has not been previously reported. We tested the hypothesis that individuals with 17q12DS have altered T-cell function, contributing to recurrent infections and atopy. Methods Alteration of CD4 + T-cell functions was assessed on FACS sorted CD4 + T-cells using RNA-seq analysis, and flow cytometry and multiplex assays. Findings We found that individuals with 17q12DS had a substantially decreased frequency of CD4 + T-cells producing the T helper (Th) 1 cytokine IFN-γ but not Th2 and Th17 cytokines when compared to age-matched healthy controls (HCs). RNA-seq analysis of CD4 + T-cells from subjects with 17q12DS, when compared to HCs, revealed decreased levels of TBX21 encoding the Th1 transcription factor T-bet, IFNG, and other Th1 chemokine genes. These findings were validated using flow cytometry and multiplex assay. Interpretation Our study is the first to demonstrate immune alterations in 17q12DS characterized by decreased T-bet and its downstream effector cytokines such as IFN-γ. These findings warrant further investigation into underlying mechanisms, which would inform precision therapy for individuals with 17q12DS. Funding National Institutes of Health KL2 TR001862 to JJS, T35DK104689 to AG, 5T32AR007107 to JPY and LO, 1R01AG056728 to IK, and 1R21AI161838 to IK and JJS.","journal":"EBioMedicine","year":2025,"id":561241,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9461,"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":670685,"name":"Hyeon Jun Shin","orcid":"0000-0002-2150-5011","position":1,"is_corresponding":false},{"id":1463684,"name":"Alan Gutierrez","orcid":null,"position":2,"is_corresponding":false},{"id":1412184,"name":"Noelle Yoo","orcid":null,"position":3,"is_corresponding":false},{"id":79010,"name":"Jennefer Par‐Young","orcid":null,"position":4,"is_corresponding":false},{"id":78985,"name":"Lais Osmani","orcid":"0000-0001-7131-390X","position":5,"is_corresponding":false},{"id":79007,"name":"Min Sun Shin","orcid":"0000-0003-2516-9251","position":6,"is_corresponding":false},{"id":278331,"name":"Pedro A. Sanchez‐Lara","orcid":"0000-0003-1181-7828","position":7,"is_corresponding":false},{"id":79005,"name":"Richard Bucala","orcid":"0000-0001-5783-5736","position":8,"is_corresponding":false},{"id":792304,"name":"Gary Soffer","orcid":"0000-0003-1641-3136","position":9,"is_corresponding":false},{"id":408961,"name":"Insoo Kang","orcid":"0000-0001-7483-1171","position":10,"is_corresponding":false},{"id":1463450,"name":"Joyce Shin","orcid":"0000-0002-4765-7988","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:58.259104Z","pmid":"39891996","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":[]}