MicroRNA-130a Contributes to Type-2 Classical DC-activation in Sjögren's Syndrome by Targeting Mitogen- and Stress-Activated Protein Kinase-1
| العنوان: | MicroRNA-130a Contributes to Type-2 Classical DC-activation in Sjögren's Syndrome by Targeting Mitogen- and Stress-Activated Protein Kinase-1 |
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| المؤلفون: | Ana P. Lopes, Joel A. G. van Roon, Sofie L. M. Blokland, Maojie Wang, Eleni Chouri, Sarita A. Y. Hartgring, Kim M. G. van der Wurff-Jacobs, Aike A. Kruize, Boudewijn M. T. Burgering, Marzia Rossato, Timothy R. D. J. Radstake, Maarten R. Hillen |
| المصدر: | Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology Frontiers in Immunology, 10(JUN). Frontiers Media S. A. |
| بيانات النشر: | Frontiers Media S.A., 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, lcsh:Immunologic diseases. Allergy, BDCA1+myeloid DC, MSK1, medicine.medical_treatment, Immunology, Primary Sjögren’s syndrome, BDCA1+ myeloid DC, primary Sjogren's syndrome, conventional dendritic cell, miR-130a, microRNA, primary Sjögren's syndrome, Ribosomal Protein S6 Kinases, 90-kDa, 03 medical and health sciences, 0302 clinical medicine, Mediator, Stable isotope labeling by amino acids in cell culture, Journal Article, medicine, Immunology and Allergy, Humans, Conventional dendritic cell, Original Research, Aged, Cyclin-dependent kinase 1, biology, Chemistry, Dendritic Cells, MiR-130a, Middle Aged, MicroRNAs, 030104 developmental biology, Cytokine, HEK293 Cells, Sjogren's Syndrome, Mitogen-activated protein kinase, Cancer research, biology.protein, Cytokines, Female, Cell activation, lcsh:RC581-607, Intracellular, 030215 immunology |
| الوصف: | Objectives: Considering the critical role of microRNAs (miRNAs) in regulation of cell activation, we investigated their role in circulating type-2 conventional dendritic cells (cDC2s) of patients with primary Sjögren’s syndrome (pSS) compared to healthy controls (HC). Methods: CD1c-expressing cDC2s were isolated from peripheral blood. A discovery cohort (15 pSS, 6 HC) was used to screen the expression of 758 miRNAs and a replication cohort (15 pSS, 11 HC) was used to confirm differential expression of 18 identified targets. Novel targets for two replicated miRNAs were identified by SILAC in HEK-293T cells and validated in primary cDC2s. Differences in cytokine production between pSS and HC cDC2s were evaluated by intracellular flow-cytometry. cDC2s were cultured in the presence of MSK1-inhibitors to investigate their effect on cytokine production. Results: Expression of miR-130a and miR-708 was significantly decreased in cDC2s from pSS patients compared to HC in both cohorts, and both miRNAs were downregulated upon stimulation via endosomal TLRs. Upstream mediator of cytokine production MSK1 was identified as a novel target of miR-130a and overexpression of miR-130a reduced MSK1 expression in cDC2s. pSS cDC2s showed higher MSK1 expression and an increased fraction of IL-12 and TNF-α-producing cells. MSK1-inhibition reduced cDC2 activation and production of IL-12, TNF-α, and IL-6. Conclusions: The decreased expression of miR-130a and miR-708 in pSS cDC2s seems to reflect cell activation. miR-130a targets MSK1, which regulates pro-inflammatory cytokine production, and we provide proof-of-concept for MSK1-inhibition as a therapeutic avenue to impede cDC2 activity in pSS. |
| وصف الملف: | image/pdf |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4b99a44915430cc71054f72025c54e2Test https://www.frontiersin.org/article/10.3389/fimmu.2019.01335/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a4b99a44915430cc71054f72025c54e2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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