Tetrahedral Framework Nucleic Acids Reestablish Immune Tolerance and Restore Saliva Secretion in a Sjögren’s Syndrome Mouse Model

2021 ◽  
Author(s):  
Shaojingya Gao ◽  
Yun Wang ◽  
Yanjing Li ◽  
Dexuan Xiao ◽  
Yunfeng Lin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Nucleic Acids ◽  
Sjögren’S Syndrome ◽  
Immune Tolerance ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Tetrahedral Framework ◽  
Saliva Secretion ◽  
Sjögren‘S Syndrome

scholarly journals Aspirin Triggered Resolvin D1 reduces inflammation and restores saliva secretion in a Sjögren’s syndrome mouse model

Rheumatology ◽  
2019 ◽  
Vol 58 (7) ◽  
pp. 1285-1292 ◽  
Author(s):  
Spencer Dean ◽  
Ching-Shuen Wang ◽  
Kihoon Nam ◽  
Christina L Maruyama ◽  
Bryan G Trump ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Resolvin D1 ◽  
Saliva Secretion ◽  
Sjögren‘S Syndrome

scholarly journals Dysregulated co-stimulatory molecule expression in a Sjögren’s syndrome mouse model with potential implications by microRNA-146a

2015 ◽  
Vol 68 (2) ◽  
pp. 606-616 ◽  
Author(s):  
Adrienne E. Gauna ◽  
Yun-Jong Park ◽  
Gautam Nayar ◽  
Marelys Onate ◽  
Jun-o Jin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

scholarly journals Imbalanced Rab3D versus Rab27 increases cathepsin S secretion from lacrimal acini in a mouse model of Sjögren's Syndrome

2016 ◽  
Vol 310 (11) ◽  
pp. C942-C954 ◽  
Author(s):  
Zhen Meng ◽  
Maria C. Edman ◽  
Pang-Yu Hsueh ◽  
Chiao-Yu Chen ◽  
Wannita Klinngam ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Cathepsin S ◽  
Secretory Vesicles ◽  
Structured Illumination Microscopy ◽  
Tear Proteins ◽  
Sjögren‘S Syndrome

The mechanism responsible for the altered spectrum of tear proteins secreted by lacrimal gland acinar cells (LGAC) in patients with Sjögren's Syndrome (SS) remains unknown. We have previously identified increased cathepsin S (CTSS) activity as a unique characteristic of tears of patients with SS. Here, we investigated the role of Rab3D, Rab27a, and Rab27b proteins in the enhanced release of CTSS from LGAC. Similar to patients with SS and to the male nonobese diabetic (NOD) mouse model of SS, CTSS activity was elevated in tears of mice lacking Rab3D. Findings of lower gene expression and altered localization of Rab3D in NOD LGAC reinforce a role for Rab3D in suppressing excess CTSS release under physiological conditions. However, CTSS activity was significantly reduced in tears of mice lacking Rab27 isoforms. The reliance of CTSS secretion on Rab27 activity was supported by in vitro findings that newly synthesized CTSS was detected in and secreted from Rab27-enriched secretory vesicles and that expression of dominant negative Rab27b reduced carbachol-stimulated secretion of CTSS in cultured LGAC. High-resolution 3D-structured illumination microscopy revealed microdomains of Rab3D and Rab27 isoforms on the same secretory vesicles but present in different proportions on different vesicles, suggesting that changes in their relative association with secretory vesicles may tailor the vesicle contents. We propose that a loss of Rab3D from secretory vesicles, leading to disproportionate Rab27-to-Rab3D activity, may contribute to the enhanced release of CTSS in tears of patients with SS.

scholarly journals Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren’s Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bo Hai ◽  
Taeko Shigemoto-Kuroda ◽  
Qingguo Zhao ◽  
Ryang Hwa Lee ◽  
Fei Liu
Keyword(s):  
Mouse Model ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Extracellular Vesicles ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Bioactive Molecules ◽  
Lymphocyte Infiltration ◽  
Sjögren‘S Syndrome

No effective treatment for Sjögren’s syndrome (SS), a chronic autoimmune disease affecting mainly salivary and lacrimal glands, is available now. Systemic infusion of allogeneic mesenchymal stem cells (MSCs) isolated from tissues such as bone marrow (BM) alleviated SS in mouse models and a small clinical trial, but further research and application of this MSC therapy were hindered by limited expandability, significant donor variations, and safety concerns of tissue-derived MSCs. To circumvent these issues, we derived MSCs from human iPSCs using an optimized protocol that can be easily scaled up to produce a huge amount of standardized MSCs. Our iPSC-MSCs inhibited the onset of lymphocyte infiltration into salivary glands in the NOD mouse model of SS in the same way as BM-MSCs. Extracellular vesicles (EVs) carry bioactive molecules in the same way as their originating cells and are more stable and considered much safer than cells for therapies. We found that EVs derived from BM-MSCs and iPSC-MSCs suppressed activation of immune cells and expression of proinflammation factors essential for SS progression in vitro and that infusion of iPSC-MSC EVs at the predisease stage decreased the lymphocyte infiltration in salivary glands and serum autoantibody levels in the same way as infusion of BM-MSCs and iPSC-MSCs. These data suggested that iPSC-MSC EVs have the potential to prevent the progression of SS before the onset of sialadenitis.

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