A Study On The Role And Mechanism Of Bone Marrow Dendritic Cells Loaded With Phosphocholine In The Progression Of Atherosclerosis

Background: Atherosclerosis(Atherosclerosis,AS)is an inflammatory disease,involves the activation antigen of adaptive and innate immune responses,including oxidized low density lipoprotein(ox LDL)and phosphorylated choline(PC)dendritic cells(DCs)antigen stimulation after activation,by presenting antigen and activate T cells,participate in the development of Atherosclerosis However,choline phosphate can promote atherosclerosis by activation of DCs and its mechanism is unclear.Methods and Results: In order to evaluate whether phosphocholine promotes atherosclerosis through DCs,2×105 DCs(DCs+PC-KLH)activated by phosphocholine keyhole hemocyanin were injected into Apo E-/-mouse model through tail vein.The area and stability of aortic sinus plaque were measured.The effects of DCs+PC-KLH on Th1,Th2,Th17,Treg,B cells and key cell types in humoral immunity were determined by flow cytometry.Compared with the control group,the area of atherosclerotic plaque in the mice injected with DCs+PC-KLH was significantly larger,the inflammation of the lesion site was increased,and the plaque instability was enhanced.In addition,flow cytometry was used to detect the phenotype of DCs in each group,and it was found that DCs+PC-KLH showed inflammatory phenotype,and its CD86,CD40 and major histocompatibility complex II class molecules(MHC-Ⅱ)increased.After co-culture of bone marrow-derived DCs and na (?) ve T cells from different groups,in vivo and in vitro experiments showed that DCs+PC-KLH promoted the differentiation of PC-specific helper T cells(Th)-1 and Th17 cells.Finally,we also found that two weeks after transfection of DCs+PC-KLH to Apo E-/-mice,it could promote the production of PC and ox LDL specific Ig G2 a,but not in the control group,indicating that DCs+PC-KLH can also promote the progression of atherosclerosis by mediating the production of specific antibodies in humoral immunity.Conclusions: These results indicate that DCs presented with PC can mediate the specific cellular and humoral immunity of PC,promote the inflammatory response of AS lesions and the progression of the disease,which may be one of the important mechanisms of atherosclerosis progression.