Depletion of microRNA-183-96-182 miRNA cluster in lymphocytes suppresses anti-dsDNA autoantibody production and IgG deposition in kidney in C57BL/6-Faslpr/lpr mice
| العنوان: | Depletion of microRNA-183-96-182 miRNA cluster in lymphocytes suppresses anti-dsDNA autoantibody production and IgG deposition in kidney in C57BL/6-Faslpr/lpr mice |
|---|---|
| المؤلفون: | Zhuang Wang, Bettina Heid, Jingjing Ren, Michael R Edwards, Thomas E. Cecere, Ran Lu, Deena Khan, David Kirsch, Christopher M. Reilly, Rujuan Dai, S. Ansar Ahmed |
| المصدر: | The Journal of Immunology. 206:25.11-25.11 |
| بيانات النشر: | The American Association of Immunologists, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | The miR-183-96-182 (miR-183C) is a highly conserved miRNA cluster among species. Our previous work found a significant upregulation of miR-183C in the splenic cells of three different murine models of systemic lupus erythematosus (SLE). Current studies revealed that miR-183C miRNAs are critically involved in immunity and autoimmunity. In this study, we found that inhibition of miR-182 alone or miR-183C in vitro with antagomirs significantly reduced lupus-related inflammatory cytokine IFN-γ and IL-6 in activated splenocytes from MRL or MRL/lpr mice. To further characterize the pathogenic role of miR-182 and miR-183C in lupus in vivo, we developed B6-lpr mice with conditional depletion of miR-182 or miR-183C in CD2+ lymphocyte. We found that depletion of either miR-182 or miR-183C in the lymphocytes of B6/lpr mice had no obvious effect on T and B cell development as similar percentage of CD4+. CD8+, CD19+, as well as Tregs, follicular helper T (TFH), germinal center B (GCB), and plasma cells were observed in the miR-182−/− and miR-183C−/− and their respective control. Importantly, we observed a significant reduction of serum anti-dsDNA autoantibodies in miR-183C−/− mice when compared to age-matched controls and the B6/lpr mice with miR-182 or miR-183C deficiency have significantly reduced IgG deposition in the kidneys. Meanwhile, there was reduced IFN production in ex vivo activated splenocytes from the knockout mice. Furthermore, we demonstrated that miR-182 and miR-183C regulated the inflammatory response in splenocytes via targeting forkhead box O1 (Foxo1). Together, our data suggest a potential therapeutic effect of targeting miR-183C in lupus. |
| تدمد: | 1550-6606 0022-1767 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::ccc8ab92c182aa6f245ab4decbcbc160 https://doi.org/10.4049/jimmunol.206.supp.25.11 |
| رقم الأكسشن: | edsair.doi...........ccc8ab92c182aa6f245ab4decbcbc160 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
|---|