Deniz Genç1, Merve Sezer Kürkçü2, Burcu Günaydin3, Emine Figen Tarhan4. 1. Department of Pediatric Health and Diseases, Faculty of Health Sciences, Muğla Sıtkı Koçman University, Muğla, Turkey 2. Research Laboratories Center, Muğla Sıtkı Koçman University, Muğla, Turkey 3. Department of Histology and Embryology, Institute of Health Sciences, Muğla Sıtkı Koçman University, Muğla, Turkey 4. Department of Rheumatology, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla, Turkey
Abstract
Background/aim: A correlation between vitamin D deficiency and primary Sjögren’s syndrome (pSS) has already been described. The limited data has been reported regarding the pathological relevance of vitamin D in primary Sjögren’s syndrome. In this study, the peripheral blood mononuclear cells were cocultured with 1,25-dihydroxyvitamin D3 to determine the modulatory effect of vitamin D3 on T and B lymphocyte phenotypes in pSS. Materials and methods: Venous blood samples were collected from 11 patients in the treatment phase and 9 drug-naive pSS patients. Peripheral blood mononuclear cells (PBMC) were isolated and separately cultured in the presence and absence of 1,25-dihydroxyvitamin D3 (10 mM) for 5 days of culture period. Lymphocyte proliferation was analyzed for CFSE signaling via flow cytometry. CD3+CD4+ cells were analyzed for intracellular IFN- and IL-17 expressions. CD19+IgD cells were analyzed for CD38 and CD27 expressions to evaluate naive and total memory B cell subsets. Culture supernatants were analyzed for the IFN-, IL-17, and IL-10 cytokine secretions via flow cytometry. Results: 1,25-dihydroxyvitamin D3 significantly decreased Th lymphocyte proliferative responses in drug-naive (p < 0.005) and treated pSS patients (p < 0.05), and B lymphocyte proliferation in drug-naive pSS PBMC cultures (p < 0.01) compared to mononuclear cell cultures alone. 1,25-dihydroxyvitamin D3 significantly decreased IFN- and IL-17 secreting Th cells in both drug naive (p < 0.005 and p < 0.01, respectively) and treated subjects (p < 0.05 and p < 0.05, respectively) by increasing FoxP3 expressing CD4+CD25+ Treg cell frequency. Plasma B lymphocytes significantly reduced in the presence of 1,25-dihydroxyvitamin D3 in drug naive pSS (p < 0.001) and treated patients (p < 0.05) mononuclear cell cultures compared to PBMC cultures alone. Total memory B cell subsets significantly increased with 1,25-dihydroxyvitamin D3 in drug naive pSS when compared with PBMC cultures alone (p < 0.005). IFN- and IL-17 cytokine levels in culture supernatants significantly reduced (p < 0.05 and p < 0.01, respectively) in drug naive pSS patients’ PBMC cultures with 1,25-dihydroxyvitamin D3, and IL-10 levels significantly enhanced in both drug-naive (p < 0.01) and treated pSS patients’ PBMC cultures (p < 0.01) in the presence of 1,25-dihydroxyvitamin D3. Conclusion: In conclusion, 1,25-dihydroxyvitamin D3 regulated immune responses in both treated and drug-naive pSS patients, but have a more pronounced modulatory effect on mononuclear cell responses in drug-naive pSS patients. This work is licensed under a Creative Commons Attribution 4.0 International License.
Background/aim: A correlation between vitamin D deficiency and primary Sjögren’s syndrome (pSS) has already been described. The limited data has been reported regarding the pathological relevance of vitamin D in primary Sjögren’s syndrome. In this study, the peripheral blood mononuclear cells were cocultured with 1,25-dihydroxyvitamin D3 to determine the modulatory effect of vitamin D3 on T and B lymphocyte phenotypes in pSS. Materials and methods: Venous blood samples were collected from 11 patients in the treatment phase and 9 drug-naive pSS patients. Peripheral blood mononuclear cells (PBMC) were isolated and separately cultured in the presence and absence of 1,25-dihydroxyvitamin D3 (10 mM) for 5 days of culture period. Lymphocyte proliferation was analyzed for CFSE signaling via flow cytometry. CD3+CD4+ cells were analyzed for intracellular IFN- and IL-17 expressions. CD19+IgD cells were analyzed for CD38 and CD27 expressions to evaluate naive and total memory B cell subsets. Culture supernatants were analyzed for the IFN-, IL-17, and IL-10 cytokine secretions via flow cytometry. Results: 1,25-dihydroxyvitamin D3 significantly decreased Th lymphocyte proliferative responses in drug-naive (p < 0.005) and treated pSS patients (p < 0.05), and B lymphocyte proliferation in drug-naive pSS PBMC cultures (p < 0.01) compared to mononuclear cell cultures alone. 1,25-dihydroxyvitamin D3 significantly decreased IFN- and IL-17 secreting Th cells in both drug naive (p < 0.005 and p < 0.01, respectively) and treated subjects (p < 0.05 and p < 0.05, respectively) by increasing FoxP3 expressing CD4+CD25+ Treg cell frequency. Plasma B lymphocytes significantly reduced in the presence of 1,25-dihydroxyvitamin D3 in drug naive pSS (p < 0.001) and treated patients (p < 0.05) mononuclear cell cultures compared to PBMC cultures alone. Total memory B cell subsets significantly increased with 1,25-dihydroxyvitamin D3 in drug naive pSS when compared with PBMC cultures alone (p < 0.005). IFN- and IL-17 cytokine levels in culture supernatants significantly reduced (p < 0.05 and p < 0.01, respectively) in drug naive pSS patients’ PBMC cultures with 1,25-dihydroxyvitamin D3, and IL-10 levels significantly enhanced in both drug-naive (p < 0.01) and treated pSS patients’ PBMC cultures (p < 0.01) in the presence of 1,25-dihydroxyvitamin D3. Conclusion: In conclusion, 1,25-dihydroxyvitamin D3 regulated immune responses in both treated and drug-naive pSS patients, but have a more pronounced modulatory effect on mononuclear cell responses in drug-naive pSS patients. This work is licensed under a Creative Commons Attribution 4.0 International License.