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Int. J. Mol. Sci. 2016, 17(8), 1282; doi:10.3390/ijms17081282

MicroRNA-155 Mediates Augmented CD40 Expression in Bone Marrow Derived Plasmacytoid Dendritic Cells in Symptomatic Lupus-Prone NZB/W F1 Mice

1
Departments of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
2
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
3
Departments of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
*
Authors to whom correspondence should be addressed.
Academic Editors: Y-h. Taguchi and Kumiko UI-TEI
Received: 6 July 2016 / Revised: 23 July 2016 / Accepted: 2 August 2016 / Published: 6 August 2016
(This article belongs to the Special Issue microRNA Regulation 2017)
View Full-Text   |   Download PDF [2359 KB, uploaded 16 August 2016]   |  

Abstract

Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by hyperactivated immune responses to self-antigens and persistent systemic inflammation. Previously, we reported abnormalities in circulating and bone marrow (BM)-derived plasmacytoid dendritic cells (pDCs) from SLE patients. Here, we aim to seek for potential regulators that mediate functional aberrations of pDCs in SLE. BM-derived pDCs from NZB/W F1 mice before and after the disease onset were compared for toll-like receptor (TLR) induced responses and microRNA profile changes. While pDCs derived from symptomatic mice were phenotypically comparable to pre-symptomatic ones, functionally they exhibited hypersensitivity to TLR7 but not TLR9 stimulation, as represented by the elevated upregulation of CD40, CD86 and MHC class II molecules upon R837 stimulation. Upregulated induction of miR-155 in symptomatic pDCs following TLR7 stimulation was observed. Transfection of miR-155 mimics in pre-symptomatic pDCs induced an augmented expression of Cd40, which is consistent with the increased CD40 expression in symptomatic pDCs. Overall, our results provide evidence for miR-155-mediated regulation in pDC functional abnormalities in SLE. Findings from this study contribute to a better understanding of SLE pathogenesis and ignite future interests in evaluating the molecular regulation in autoimmunity. View Full-Text
Keywords: systemic lupus erythematosus; plasmacytoid dendritic cells; microRNAs; toll-like receptor 7 systemic lupus erythematosus; plasmacytoid dendritic cells; microRNAs; toll-like receptor 7
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Yan, S.; Yim, L.Y.; Tam, R.C.Y.; Chan, A.; Lu, L.; Lau, C.S.; Chan, V.S.-F. MicroRNA-155 Mediates Augmented CD40 Expression in Bone Marrow Derived Plasmacytoid Dendritic Cells in Symptomatic Lupus-Prone NZB/W F1 Mice. Int. J. Mol. Sci. 2016, 17, 1282.

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