{"doi":"10.1126/scitranslmed.ado4856","title":"IFN-γ–producing T <sub>H</sub> 1 cells and dysfunctional regulatory T cells contribute to the pathogenesis of Sjögren’s disease","abstract":"Sjögren’s disease (SjD) is an autoimmune disorder characterized by progressive salivary and lacrimal gland dysfunction, inflammation, and destruction, as well as extraglandular manifestations. SjD is associated with autoreactive B and T cells, but its pathophysiology remains incompletely understood. Abnormalities in regulatory T (T reg ) cells occur in several autoimmune diseases, but their role in SjD is ambiguous. We had previously shown that the function and development of T reg cells depend on store-operated Ca 2+ entry (SOCE), which is mediated by ORAI1 Ca 2+ channels and stromal interaction protein 1 (STIM1) and STIM2. Here, we show that mice with a Foxp3 + T reg cell–specific deletion of Stim1 and Stim2 develop a phenotype that fulfills all classification criteria of human SjD. Mutant mice have salivary and lacrimal gland inflammation characterized by strong lymphocyte infiltration and transcriptional signatures dominated by T helper 1 (T H 1) and interferon (IFN) signaling. CD4 + T cells from mutant mice are sufficient to induce SjD-like disease in an IFN-γ–dependent manner. Inhibition of IFN signaling with the JAK1/2 inhibitor baricitinib alleviated CD4 + T cell–induced SjD in mice. These findings are consistent with the transcriptional profiles of CD4 + T cells from patients with SjD, which indicate enhanced T H 1 but reduced memory T reg cell function. Together, our study provides evidence for a critical role of dysfunctional T reg cells and IFN-γ–producing T H 1 cells in the pathogenesis of SjD.","journal":"Science Translational Medicine","year":2024,"id":420334,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"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":882402,"name":"Wenyi Li","orcid":"0000-0002-5436-1317","position":1,"is_corresponding":false},{"id":1002353,"name":"Maxwell McDermott","orcid":"0009-0005-9503-0556","position":2,"is_corresponding":false},{"id":457710,"name":"Ga‐Yeon Son","orcid":"0000-0002-3680-9421","position":3,"is_corresponding":false},{"id":311502,"name":"George Maiti","orcid":"0000-0002-6701-5499","position":4,"is_corresponding":false},{"id":715317,"name":"Fang Zhou","orcid":"0000-0002-5542-2994","position":5,"is_corresponding":false},{"id":882401,"name":"Anthony Tao","orcid":"0000-0003-0978-2769","position":6,"is_corresponding":false},{"id":325424,"name":"Dimitrius Raphael","orcid":"0000-0003-1064-3010","position":7,"is_corresponding":false},{"id":71267,"name":"André L. Moreira","orcid":"0000-0003-1857-3774","position":8,"is_corresponding":false},{"id":1211727,"name":"Boheng Shen","orcid":null,"position":9,"is_corresponding":false},{"id":244370,"name":"Martin Vaeth","orcid":"0000-0001-8974-7052","position":10,"is_corresponding":false},{"id":650269,"name":"Bettina Nadorp","orcid":"0000-0003-1974-8425","position":11,"is_corresponding":false},{"id":311505,"name":"Shukti Chakravarti","orcid":"0000-0001-7543-1903","position":12,"is_corresponding":false},{"id":426400,"name":"Rodrigo S. Lacruz","orcid":"0000-0002-0776-6143","position":13,"is_corresponding":false},{"id":244372,"name":"Stefan Feske","orcid":"0000-0001-5431-8178","position":14,"is_corresponding":false},{"id":815116,"name":"Yin‐Hu Wang","orcid":"0000-0002-3637-8852","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T01:57:25.777459Z","pmid":"39693412","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":[]}