{"doi":"10.3389/fimmu.2020.01129","title":"T-bet Expression in Peripheral Th17.0 Cells Is Associated With Pulmonary Function Changes in Sarcoidosis","abstract":"Background: Interferon-gamma (IFN-γ) is a key mediator of sarcoidosis-related granulomatous inflammation. Previous findings of IFN-γ-producing Th17 cells in bronchoalveolar lavage fluid from sarcoidosis patients invokes the transition of Th17.0 cells to Th17.1 cells in the disease’s pathogenesis. Since the T bet transcription factor is crucial for this transition, the goal of this study was to determine if T bet expression in Th17.0 cells reflects the extent of granulomatous inflammation in sarcoidosis patients as assessed by clinical outcomes. Methods: Using a case-control study design, we identified two groups of sarcoidosis subjects (total N=43) with pulmonary function tests (PFTs) that either 1) changed (increased or decreased) longitudinally or 2) were stable. We used flow cytometry to measure the transcription factors T bet and RORγt in Th1, Th17.0, and Th17.1 cell subsets defined by CCR6, CCR4 and CXCR3 in blood samples. We compared the percentages of T bet+ cells in RORγt+Th17.0 cells (defined as CCR6+CCR4+CXCR3-) based on subjects’ PFT group. We also assessed the relationship between the direction of change in PFTs with the changes in %T bet+ frequencies using mixed effects modeling. Results: We found that T bet expression in subjects’ RORγt+Th17.0 cells varied based on clinical outcome. The T bet+ percentage of RORγt+Th17.0 cells was higher in the cases (subject group with PFT changes) as compared to controls (stable group) (27% vs. 16%, p = 0.0040). In comparisons before and after subjects’ PFT changes, the T bet+ frequency of RORγt+Th17.0 cells increased or decreased in the opposite direction of the PFT change. The percentage of these T bet+ cells was also higher in those with greater numbers of involved organs. Serum levels of interferon-γ-induced chemokines, CXCL9, CXCL10, and CXCL11, and whole blood gene expression of IFN-γ-related genes including GBP1, TAP1, and JAK2 were independently positively associated with the T bet+ frequencies of RORγt+Th17.0 cells. Conclusions: These data suggest that expression of T bet in Th17.0 cells could reflect the extent of granulomatous inflammation in sarcoidosis patients because they represent a transition state leading to the Th17.1 cell phenotype. These findings indicate that Th17 plasticity may be part of the disease paradigm.","journal":"Frontiers in Immunology","year":2020,"id":79531,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"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":413329,"name":"Siddharth Machiraju","orcid":"0000-0002-2396-5986","position":1,"is_corresponding":false},{"id":351751,"name":"Isabel Elaine Allen","orcid":"0000-0001-9029-9744","position":2,"is_corresponding":false},{"id":250097,"name":"Prescott G. Woodruff","orcid":"0000-0003-3176-0603","position":3,"is_corresponding":false},{"id":413330,"name":"Laura L. Koth","orcid":"0000-0001-9541-3622","position":4,"is_corresponding":false},{"id":414740,"name":"N. Arger","orcid":null,"position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T21:50:57.971597Z","pmid":"32774332","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":[]}