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

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Peng Zhang ◽  
Ru-Tao Liu ◽  
Tong Du ◽  
Chun-Lin Yang ◽  
Yu-Dong Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Myasthenia Gravis ◽  
Stromal Cells ◽  
Experimental Autoimmune Myasthenia Gravis ◽  
Autoimmune Myasthenia ◽  
Thymic Stromal Cells ◽  
Experimental Autoimmune

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.

scholarly journals Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis.

1978 ◽  
Vol 147 (4) ◽  
pp. 973-983 ◽  
Author(s):  
V A Lennon ◽  
M E Seybold ◽  
J M Lindstrom ◽  
C Cochrane ◽  
R Ulevitch
Keyword(s):  
Myasthenia Gravis ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Neuromuscular Transmission ◽  
Passive Transfer ◽  
Experimental Autoimmune Myasthenia Gravis ◽  
Autoimmune Myasthenia ◽  
Experimental Autoimmune

An acute phase of experimental autoimmune myasthenia gravis (EAMG) occurs transiently early in the immune response of Lewis rats to nicotinic acetylcholine receptors (AChR) when Bordetella pertussis is used as adjuvant. It is characterized by a destructive cellular attack directed at the postsynaptic membranes of muscle. Acute EAMG can be passively transferred to normal rats by IgG from serum of rats with chronic EAMG. In the present study, acute EAMG, induced either by passive transfer of syngeneic antibodies or by active immmunization, was inhibited in rats depleted of complement by treatment with cobra venom factor (CoF). Furthermore, passive transfer of antibodies in excess of the muscle's content of AChR was without any measurable effect in rats treated with CoF. Although 60% of the muscle's AChR was complexed with antibody, there was no reduction in the muscle's content of AChR, and neuromuscular transmission was not compromised as judged electromyographically by curare sensitivity. These data imply that redistribution, accelerated degradation, and impairment of the ionophore function of AChR, effects of antibodies described in vitro on extrajunctional AChR, do not play a significant role in vivo in impairing neuromuscular transmission in an intact neuromuscular junction. Complement appears to be a critical mediator of anti-AChR antibodies' pathogenicity in vivo.

scholarly journals CXCR5-negative natural killer cells ameliorate experimental autoimmune myasthenia gravis by suppressing follicular helper T cells

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Chun-Lin Yang ◽  
Peng Zhang ◽  
Ru-Tao Liu ◽  
Na Zhang ◽  
Min Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Myasthenia Gravis ◽  
Nk Cells ◽  
Ex Vivo ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Experimental Autoimmune Myasthenia Gravis ◽  
Autoimmune Myasthenia ◽  
Experimental Autoimmune ◽  
Cell Zone

Abstract Background Recent studies have demonstrated that natural killer (NK) cells can modulate other immune components and are involved in the development or progression of several autoimmune diseases. However, the roles and mechanisms of NK cells in regulating experimental autoimmune myasthenia gravis (EAMG) remained to be illustrated. Methods To address the function of NK cells in experimental autoimmune myasthenia gravis in vivo, EAMG rats were adoptively transferred with splenic NK cells. The serum antibodies, and splenic follicular helper T (Tfh) cells and germinal center B cells were determined by ELISA and flow cytometry. The roles of NK cells in regulating Tfh cells were further verified in vitro by co-culturing splenocytes or isolated T cells with NK cells. Moreover, the phenotype, localization, and function differences between different NK cell subtypes were determined by flow cytometry, immunofluorescence, and ex vivo co-culturation. Results In this study, we found that adoptive transfer of NK cells ameliorated EAMG symptoms by suppressing Tfh cells and germinal center B cells. Ex vivo studies indicated NK cells inhibited CD4+ T cells and Tfh cells by inducing the apoptosis of T cells. More importantly, NK cells could be divided into CXCR5- and CXCR5+ NK subtypes according to the expression of CXCR5 molecular. Compared with CXCR5- NK cells, which were mainly localized outside B cell zone, CXCR5+ NK were concentrated in the B cell zone and exhibited higher expression levels of IL-17 and ICOS, and lower expression level of CD27. Ex vivo studies indicated it was CXCR5- NK cells not CXCR5+ NK cells that suppressed CD4+ T cells and Tfh cells. Further analysis revealed that, compared with CXCR5- NK cells, CXCR5+ NK cells enhanced the ICOS expression of Tfh cells. Conclusions These findings highlight the different roles of CXCR5- NK cells and CXCR5+ NK cells. It was CXCR5- NK cells but not CXCR5+ NK cells that suppressed Tfh cells and inhibited the autoimmune response in EAMG models.

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