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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2019

Open Access 01-12-2019 | Myasthenia Gravis | Research

Exosomes derived from statin-modified bone marrow dendritic cells increase thymus-derived natural regulatory T cells in experimental autoimmune myasthenia gravis

Authors: Peng Zhang, Ru-Tao Liu, Tong Du, Chun-Lin Yang, Yu-Dong Liu, Meng-Ru Ge, Min Zhang, Xiao-Li Li, Heng Li, Ying-Chun Dou, Rui-Sheng Duan

Published in: Journal of Neuroinflammation | Issue 1/2019

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Abstract

Background

The thymus plays an essential role in the pathogenesis of myasthenia gravis (MG). In patients with MG, natural regulatory T cells (nTreg), a subpopulation of T cells that maintain tolerance to self-antigens, are severely impaired in the thymuses. In our previous study, upregulated nTreg cells were observed in the thymuses of rats in experimental autoimmune myasthenia gravis after treatment with exosomes derived from statin-modified dendritic cells (statin-Dex).

Methods

We evaluated the effects of exosomes on surface co-stimulation markers and Aire expression of different kinds of thymic stromal cells, including cTEC, mTEC, and tDCs, in EAMG rats. The isolated exosomes were examined by western blot and DLS. Immunofluorescence was used to track the exosomes in the thymus. Flow cytometry and western blot were used to analyze the expression of co-stimulatory molecules and Aire in vivo and in vitro.

Results

We confirmed the effects of statin-Dex in inducing Foxp3+ nTreg cells and found that both statin-Dex and DMSO-Dex could upregulate CD40 but only statin-Dex increased Aire expression in thymic stromal cells in vivo. Furthermore, we found that the role of statin-Dex and DMSO-Dex in the induction of Foxp3+ nTreg cells was dependent on epithelial cells in vitro.

Conclusions

We demonstrated that statin-Dex increased expression of Aire in the thymus, which may further promote the Foxp3 expression in the thymus. These findings may provide a new strategy for the treatment of myasthenia gravis.
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Metadata
Title
Exosomes derived from statin-modified bone marrow dendritic cells increase thymus-derived natural regulatory T cells in experimental autoimmune myasthenia gravis
Authors
Peng Zhang
Ru-Tao Liu
Tong Du
Chun-Lin Yang
Yu-Dong Liu
Meng-Ru Ge
Min Zhang
Xiao-Li Li
Heng Li
Ying-Chun Dou
Rui-Sheng Duan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-019-1587-0

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