T-bet Expression in Peripheral Th17.0 Cells Is Associated With Pulmonary Function Changes in Sarcoidosis
| العنوان: | T-bet Expression in Peripheral Th17.0 Cells Is Associated With Pulmonary Function Changes in Sarcoidosis |
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| المؤلفون: | Laura L. Koth, Isabel E. Allen, N. Arger, Prescott G. Woodruff, Siddharth Machiraju |
| المصدر: | Frontiers in Immunology, Vol 11 (2020) Frontiers in Immunology |
| بيانات النشر: | Frontiers Media SA, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Chemokine, CCR4, CXCR3, Th1, Pathogenesis, 0302 clinical medicine, Group F, 2.1 Biological and endogenous factors, Immunology and Allergy, Medicine, Interferon gamma, Aetiology, Lung, Original Research, medicine.diagnostic_test, biology, hemic and immune systems, Pulmonary, Nuclear Receptor Subfamily 1, Group F, Member 3, Middle Aged, Prognosis, Medical Microbiology, Female, Th17.1, RORγt, Th17, Bronchoalveolar Lavage Fluid, medicine.drug, lcsh:Immunologic diseases. Allergy, Adult, Sarcoidosis, Nuclear Receptor Subfamily 1, Member 3, Immunology, chemical and pharmacologic phenomena, T-bet, Autoimmune Disease, Interferon-gamma, 03 medical and health sciences, Sarcoidosis, Pulmonary, Clinical Research, Humans, CXCL10, CXCL11, sarcoidosis, Aged, business.industry, Inflammatory and immune system, chemokine, ROR gamma t, 030104 developmental biology, Bronchoalveolar lavage, Case-Control Studies, biology.protein, Th17 Cells, lcsh:RC581-607, T-Box Domain Proteins, business, Biomarkers, 030215 immunology |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f2302e878560f7ba39790215f284ca3Test https://doi.org/10.3389/fimmu.2020.01129Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7f2302e878560f7ba39790215f284ca3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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