The Chrysin Inhibits Dendritic Cells And Meliorates Experimental Autoimmune Encephalomyelitis

Multiple Sclerosis(MS)is a chronic ininflammatory demyelinating disease of the central nervous system.Recently,current drugs are all unsatisfactory.It is therefore necessary to develop new drugs.Experimental Autoimmune Encephalomyelitis(EAE)is an animal model of MS,and is well an important model of the basic research of autoimmune inflammatory reaction.Both MS and EAE are believed to be a myelin-specific CD4+ T cell-mediated autoimmune degenerative disease.Major is closely related to TH1 and TH17 cells.Dendritic cells(DCs)are professional antigen-presenting cells(APC)and play a crucial role in the initiation of immune responses.Immature DCs(iDCs)are very proficient at antigen uptake,while the main function of mature DCs(mDCs)is to induce T cell activation.What's more,cytokines produced by DCs are important in promoting the differentiation of TH1,TH2,TH17 and regulatory T cells.Different T cell subtypes execute different physiological functions in corresponding diseases.According to their important role in the immune system,DCs are a potential therapeutic target for the control of autoimmune and inflammatory disease.Chrysin have been approved for the treatment of cutaneous T cell lymphoma.However,the effect of chrysin on autoimmune diseases such as MS and EAE,remain incomplete.So,this is the main content of our research.Research objectives:We have evaluated the effects of chrysin on human CD14+monocyte-derived DCs and mouse immature DCs differentiation,mature in vitro.Furthermore,our research examined the actions of chrysin on EAE in vivo to characterize the role and cellular mechanism.In a word,this study explores a new therapy pathway for inflammatory diseases such as MS.Experiment contents and methods:In vitro,human CD14+ monocytes were separated from Peripheral Blood Mononuclear Cells by using a magnetic separation column,and then differentiated to DCs and induced to mature.DCs were analyzed by FACS to explore expression of surface marker.In vivo,mice were immunized with MOG to induce EAE,and chrysin was intragastric administered.Meanwhile,mice were observed and clinical scores were assessed daily.Paraffin sections of Lumbar spinal cords were stained with H&E,Luxol fast blue,immunostained with anti-CD3 and anti-F4/80.FACS was applied to detect the effect of chrysin on spleen different T cell subtypes and DC in EAE.Experimental results:In vitro,data of FACS showed that chrysin decreased expression of surface marker CD83,CD86 and HLA-DR on iDCs and mDCs.Chrysin inhibited DCs differentiation and maturation.Chrysin impaired the endocytosis function of iDCs and mDCs induced allogeneic T cell proliferation.In vivo,chrysin significant decreased disease incidence,mean clinical score,cumulative score and maximal score of EAE.H&E and luxol fast blue staining showed that lumbar spinal cords of chrysin-treated mice exhibited smaller numbers of inflammatory cells and small areas of demyelination.And immunohistochemical evaluation suggested that the numbers of infiltrating T cells and macrophages were lower in chrysin treated-mice.Chrysin suppressed pathogenic TH1 and TH17 cells,and expression of costimulatory molecules of DC in EAE mice.These results were corresponded to the effect of chrysin on human CD14+ monocyte-derived dendritic cells and mouse immatue DC.Conclusion:Chrysin suppresses human CD14+ monocyte-derived DC differentiation,maturation,.In addition,chrysin ameliorates EAE occurrence and development by inhibiting immune inflammatory response in CNS,and suppressing DC and pathogenic TH1 and TH17 cells.Chrysin has therapeutic effect on EAE.This study laid a theoretical foundation for the application of chrysin to treat inflammation related diseases such as multiple sclerosis.