{"doi":"10.1093/jleuko/qiaf183","title":"IL-36 mediates immune activation in Sjögren's disease and may represent a novel biomarker of disease","abstract":"Sjögren's disease (SjD) is a systemic autoimmune disease. The underlying disease mechanisms remain poorly understood, and there are no curative therapies. MyD88-mediated signaling is essential for SjD, although the pathways that rely on MyD88 are not well characterized. Our objective was to determine if MyD88-dependent IL-1 cytokines mediate inflammation in SjD. Using a SjD mouse model and patient samples, RNA sequencing was performed on salivary tissue and peripheral B cells. Splenocytes from SjD mice were stimulated with IL-36 cytokines and B cell activation was assessed. Finally, ELISAs were employed to measure IL-36 in SjD patient sera. Our data revealed that IL-1 family-associated genes were dysregulated in SjD salivary tissue. Salivary B cells showed upregulation of genes associated with MyD88 and IL-36 activation and peripheral B cells from SjD mice had dysregulated IL-1 signaling networks. Moreover, B cells from SjD mice showed enhanced activation when stimulated with IL-36 cytokines, and splenocytes derived from SjD mice exhibited elevated cytokine secretion. Finally, high levels of IL-36α and IL-36γ were present in SjD patient sera and IL-36α levels discriminated SjD patients from non-SjD control subjects. Therefore, IL-36 contributes to disease, and drugs targeting IL-1 cytokines, particularly IL-36, may represent novel therapeutic targets for SjD.","journal":"Journal of Leukocyte Biology","year":2025,"id":549726,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9619,"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":955364,"name":"Theresa Wrynn","orcid":null,"position":1,"is_corresponding":false},{"id":354808,"name":"Jeremy Kiripolsky","orcid":null,"position":2,"is_corresponding":false},{"id":354809,"name":"Eileen M. Kasperek","orcid":null,"position":3,"is_corresponding":false},{"id":1444860,"name":"Jeffrey C Miecznikowski","orcid":null,"position":4,"is_corresponding":false},{"id":1444861,"name":"Paola Jurado Pérez","orcid":null,"position":5,"is_corresponding":false},{"id":1287042,"name":"Joseph D. Twohig","orcid":null,"position":6,"is_corresponding":false},{"id":298802,"name":"Blake M. Warner","orcid":"0000-0002-4961-018X","position":7,"is_corresponding":false},{"id":684298,"name":"Rose-Anne Romano","orcid":null,"position":8,"is_corresponding":false},{"id":353578,"name":"Jill M. Kramer","orcid":"0000-0001-9828-8556","position":9,"is_corresponding":false},{"id":1444859,"name":"Bayan Alhaddad","orcid":null,"position":0,"is_corresponding":true}],"reference_count":104,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:12.321988Z","pmid":"41430745","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":[]}